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Description  |
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BACKGROUND OF THE INVENTION
The present invention relates to the use of certain bicyclic octane
derivatives in altering organoleptic properties, such as flavors and
aromas, and compositions suited to such uses, as well as to certain novel
bicyclic octane derivatives and processes for preparing them.
A material having the structure
##SPC1##
(dioxolane-substituted 5-isopropyl-7-methylbicyclo-[2.2.2]-oct-7 -ene) has
been sold by Societe Anonyme Des Establissements Roure Bertrand Fils Et
Justin Dupont 17 Bis Rue Legendre Paris XVII.sup.e France under the name
"Glycollierol" for use in perfumes. Dragoco, Gerberding & Co., GmbH,
Holzminden, Federal Republic of Germany has sold a material having the
structure
##SPC2##
(carbomethoxy-substituted 1,4-dimethyl-bicyclo-[2.2.2]-oct-5-ene) as a
perfume ingredient with a patchouli, vetivert type odor, under the name
"Mahogonate".
U.S. Pat. No. 2,957,906 broadly shows acyl- and carboalkoxy-substituted
bicyclooctene, among the other bicyclic compounds for pesticide and
agricultural uses, and U.S. Pat. No. 3,304,167 shows various norbornane
(bicyclo-[2.2.1]-heptane) derivatives, including nitrile derivatives and
certain of the materials are said to be herbicidally active.
Danishevsky et al, Chem. Comm. 1968, 1287, show
1,3,3-trimethyl-6-isobutylbicyclo-[2.2.2]-octan-2-one and Kealy et al, J.
Org. Chem., 26, 987 (1961) demonstrate
1,3-dimethyl-3-ethylbicyclo-[2.2.2]-octane and the corresponding
bicyclooct-5-ene. Orahovats et al, Collect. Czech. Chem. Comm., 35(3), 838
(1970) show 2-hydroxy- and 2-oxo-substituted
3-methylbicyclo-[2.2.2]-oct-5-ene and the corresponding bicyclooctane.
Organic Reactions, IV, 66 states that Diels and Alder, Ann. 478, 137
(1937) prepared bicyclo-[2.2.2]-oct-5-ene-8-carboxaldehyde and that
.alpha.-phellandrene, 2-isopropyl-5-methylbicyclo-[2.2.2]-oct-5-en-7- and
8-carboxaldehyde were prepared by Diels and Alder, Ann. 470, 62 (1929).
Morita et al, J. Org. Chem. 30, 533 (1965, show various alkylated
4-alkoxybicyclo-[2.2.2]-octan-2-ones, and Curtin et al, J. Am. Chem. Soc.
81, 622 (1959) show methylated bicyclo-[2.2.2]-oct-5-en-2-ones. Various
other bicyclo-[2.2.2]-octane materials and methods for their preparation
are demonstrated by Petrov, J. Gen. Chem. U.S.S.R. 11, 809 (1941); Selca
et al, Ber. 75, 1379 (1942); Kenyon and Young, J. Chem. Soc. 263 (1941);
Alder et al, Ann. 543,1 (1939); Tich et al, Collect. Czech. Chem. Comm.
35(2), 459 (1970); Kraus et al, Ann. 708, 127 (1967); Berson et al, J. Am.
Chem. Soc. 80, 5010 (1964); Karanskil et al, Zh. obshchei Khim. 29, 2976;
McDonald et al, J. Org. Chem. 35, 1250 (1970); Curtin et al, J. Am. Chem.
Soc. 81, 662 (1959); Conroy et al, J. Am. Chem. Soc. 75, 2530 (1953) and
78, 2290 (1957); Curtin et al, J. Am. Chem. Soc. 79, 3156 (1957); Waring
et al, J. Am. Chem. Soc. 86, 1454 (1964); Alder et al, Ber. 90, 1709
(1957); Cookson et al, J. Chem. Soc. 2302 (1956); Kamamato, Chem. Abst.
58, 2391f (1963); and Cimarusti et al, J. Am. Chem. Soc. 90, 113 (1968).
German Offenlegungsschrift 2,242,913 shows tricyclic alcohol, denominated
"nordehydro-patchoulol", extracted from patchouli alcohol. Tricyclic
compounds have also been prepared by Greuber et al, Helv. Chim. Acta 55,
526 (1972). Various preparative procedures for preparation of tricyclic
materials are exhibited by Waring et al, J. Am. Chem. Soc. 86, 1454 (1964)
and Blum et al, Synthesis No. 4, 195 (1972). Quinones and quinols have
been prepared by Chambers et al, J. Chem. Soc. (London) 1804 (1959) and
McClure, J. Org. Chem. 28, 69 (1963). Various cyclic derivatives are
demonstrated by Alder et al, Ber. 90, 1709 (1957) and Day, Chem. Rev. 53,
167 (1953).
THE INVENTION
Briefly, the present invention involves the use of certain alkylated
saturated and unsaturated derivatives of bicyclo-[2.2.2]-octane, as well
as certain novel derivatives and processes for preparing them. The
compounds for use in altering the organoleptic properties of materials can
be represented by the formula
##SPC3##
wherein the dashed lines represent single or double carbon-to-carbon bonds;
one of R.sub.2 and R.sub.3 is hydrogen or alkyl and the other is hydrogen
or hydroxy or, taken together, R.sub.2 and R.sub.3 are a carbonyl oxygen;
R.sub.4 and R.sub.5 are alkyl; R.sub.1, R.sub.6, R.sub.7, and R.sub.8 are
hydrogen or alkyl; and one of R.sub.9 and R.sub.10 is hydrogen, alkyl
cyano, carboalkoxy, or aliphatic acyl and the other is hydrogen, at least
five of R.sub.1 through R.sub.10, inclusive, being other than hydrogen.
It will be understood from the present description that when one double
bond is present, it will link the carbon atoms upon which R.sub.7 and
R.sub.8 are substituent, thus:
##SPC4##
The basic structure when there are two double bonds present is
##SPC5##
In the present disclosure, R.sub.1 through R.sub.10, inclusive, have the
meaning as aforesaid.
Desirable compounds prepared according to the present invention include:
1,3,3,4,5,6-Hexamethylbicyclo-[2.2.2]-oct-5-en-2-one with the formula
##SPC6##
1,2,3,3,4,5,6-Heptamethylbicyclo-[2.2.2]-oct-5-en-2-ol having the formula
##SPC7##
Carbomethoxylated 1,3,3,5-tetramethylbicyclo-[2.2.2]-octenes, and more
specifically the 7-carbomethoxy derivative having the formula
##SPC8##
and the 8-carbomethoxy derivative having the formula
##SPC9##
Carbomethoxy 1,3,3,5-tetramethylbicyclo-[2.2.2]-octanes, and more
specifically the 7-carbomethoxy derivative having the formula
##SPC10##
and the 8-carbomethoxy derivative having the formula
##SPC11##
The cyano derivatives of 1,3,3,5-tetramethylbicyclo-[2.2.2]-octenes, and
more specifically the 7-cyano derivative having the formula
##SPC12##
and the 8-cyano derivative having the formula
##SPC13##
The cyano derivatives of 1,3,3,5-tetramethylbicyclo-[2.2.2]-octanes, and
more specifically the 7-cyano derivative having the formula
##SPC14##
and the 8-cyano derivative having the formula
##SPC15##
The acetyl derivatives of 1,3,3,5-tetramethylbicyclo-[2.2.2]-octenes, and
more specifically the 7-acetyl derivative having the formula
##SPC16##
and the 8-acetyl derivative having the formula
##SPC17##
The isopropyl derivatives of
1,3,3-trimethylbicyclo-[2.2.2]-octa-5,7-dien-2-one, and more specifically
5-isopropyl-1,3,3-trimethylbicyclo-[2.2.2]-octa-5,7-dien-2-one having the
formula
##SPC18##
and 6-isopropyl-1,3,3-trimethylbicyclo-[2.2.2]-octa-5,7-dien-2-one having
the formula
##SPC19##
The isopropyl derivatives of 1,3,3-trimethylbicyclo-[2.2.2]-octan-2-one and
more specifically 5-isopropyl-1,3,3-trimethylbicyclo-[2.2.2]-octan-2-one
having the formula
##SPC20##
and 6-isopropyl-1,3,3-trimethylbicyclo-[2.2.2]-octan- 2-one having the
formula
##SPC21##
The isopropyl derivatives of
3,3-dimethylbicyclo-[2.2.2]-octa-5,7-dien-2-one, and more specifically
5-isopropyl-3,3-dimethylbicyclo-[2.2.2]-octa-5,7-dien-2-one having the
formula
##SPC22##
and 6-isopropyl-3,3-dimethylbicyclo-[2.2.2]-octa-5,7-dien-2-one having the
formula
##SPC23##
The isopropyl derivatives of 3,3-dimethylbicyclo-[2.2.2]-octan-2-one and
more specifically 5-isopropyl-3,3-dimethylbicyclo-[2.2.2]-octan-2-one
having the formula
##SPC24##
and 6-isopropyl-3,3-dimethylbicyclo-[2.2.2]-octan-2-one having the formula
##SPC25##
The isopropyl derivatives of 1,2,3,3-tetramethylbicyclo-[2.2.2]-octan-2-ol
and more specifically
5-isopropyl-1,2,3,3-tetramethylbicyclo-[2.2.2]-octan-2-ol having the
formula
##SPC26##
and 6-isopropyl-1,2,3,3-tetramethylbicyclo-[2.2.2]-octan-2-ol having the
formula
##SPC27##
The isopropyl derivatives of 2,3,3-trimethylbicyclo-[2.2.2]-octan-2-ol and
more specifically 5-isopropyl-2,3,3-trimethylbicyclo-[2.2.2]-octan-2-ol
having the formula
##SPC28##
and 6-isopropyl-2,3,3-trimethylbicyclo-[2.2.2]-octan-2-ol having the
formula
##SPC29##
The isopropyl derivatives of 3,3-dimethylbicyclo-[2.2.2]-oct-5-en-2-one and
more specifically 5-isopropyl-3,3-dimethylbicyclo-[2.2.2]-oct-5-en-2-one
having the formula
##SPC30##
and 6-isopropyl-3,3-dimethylbicyclo-[2.2.2]-oct-5-en-2-one having the
formula
##SPC31##
1,3,3,4,5,6-Hexamethyl-2-ethylbicyclo-[2.2.2]-oct-5-en-2-ol having the
formula
##SPC32##
1,3,3,4,5,6-Hexamethylbicyclo-[2.2.2]-oct-5-en-2-ol having the formula
##SPC33##
The methyl derivatives of
1,3,3,4,5,6-hexamethylbicyclo-[2.2.2]-oct-5-en-2-one and more specifically
1,3,3,4,5,6,7-heptamethylbicyclo-[2.2.2]-oct-5-en-2-one having the formula
##SPC34##
and 1,3,3,4,5,6,8-heptamethylbicyclo-[2.2.2]-oct-5-en-2-one having the
formula
##SPC35##
The methyl derivatives of
1,2,3,3,4,5,6-heptamethylbicyclo-[2.2.2]-oct-5-en-2-ol and more
specifically 1,2,3, 3,4,5,6,7-octamethylbicyclo-[2.2.2]-oct-5-en-2-ol
having the formula
##SPC36##
and 1,2,3,3,4,5,6,8-octamethylbicyclo-[2.2.2]-oct-5-en-2-ol having the
formula
##SPC37##
2-n-Butyl-1,3,3-trimethylbicyclo-[2.2.2]-oct-5-en-2-ol having the formula
##SPC38##
It will be apparent to those skilled in the art from the present disclosure
that the foregoing compounds can exist as various diastereoisomers and the
foregoing formulas are intended to encompass the isomeric forms of the
compounds. By way of illustration, a particularly preferred compound,
(II), can exist in the forms
##SPC39##
The foregoing representation sets forth the differences in various
diastereoisomers of (II) by way of three dimensional representations.
As taught hereinafter, the compounds of the present invention have certain
woody, precious wood and camphoraceous type odors and flavors which suit
them for altering organoleptic properties of consumable materials.
Particularly desirable materials are those in which the alkyl groups and
alkoxy groups are lower alkyl, preferably those having one to four carbon
atoms. In certain particularly preferred embodiments, R.sub.4 and R.sub.5
are methyl.
It will be appreciated from the present disclosure that the bicyclo-[2.2.2]
-octane derivatives and mixtures thereof according to the present
invention can be used to alter, vary, fortify, modify, enhance, or
otherwise improve the organoleptic properties, including aroma and/or
flavor, of a wide variety of materials which are ingested, consumed, or
otherwise organoleptically sensed. The term "alter" in its various forms
will be understood herein to mean the supplying or imparting an aroma or
flavor character or note to an otherwise bland, relatively odorless or
tasteless substance, or augmenting an existing characteristic where the
natural aroma or flavor is deficient in some regard, or supplementing the
existing aroma or flavor impression to modify the organoleptic character.
The materials which are so altered are generally referred to herein as
consumable materials.
The bicyclo-[2.2.2]-octane derivatives of this invention are accordingly
useful individually or in admixture as fragrances. They can be used to
contribute various woody, camphoraceous, patchouli or floral fragrances.
As olfactory agents, the derivatives of this invention can be formulated
into or used as components of a "perfume composition".
A perfume composition is composed of a small but effective amount of a
bicyclo-[2.2.2] -octane derivative according to this invention and an
auxiliary perfume ingredient, including, for example, alcohols, aldehydes,
ketones, nitriles, esters, and frequently hydrocarbons which are admixed
so that the combined odors of the individual components produce a pleasant
or desired fragrance. Such perfume compositions usually contain (a) the
main note or the "bouquet" or foundation-stone of the composition; (b)
modifiers which round-off and accompany the main note; (c) fixatives which
include odorous substances which lend a particular note to the perfume
throughout all stages of evaporation, and substances which retard
evaporation, and (d) top-notes which are usually low-boiling fresh
smelling materials.
In perfume compositions the individual component will contribute its
particular olfactory characteristics, but the overall effect of the
perfume composition will be the sum of the effect of each ingredient.
Thus, the individual derivatives of this invention, or mixtures thereof,
can be used to alter the aroma characteristics of a perfume composition,
for example, by high-lighting or moderating the olfactory reaction
contributed by another ingredient in the composition.
The amount of the compounds of this invention which will be effective in
perfume compositions depends on many factors, including the other
ingredients, their amounts and the effects which are desired. It has been
found that perfume compositions containing as little as 0.1 percent of the
compounds of this invention, or even less, can be used to impart a scent
odor to soaps, cosmetics, and the other products. The amount employed can
range up to five percent or higher of the fragrance components and will
depend on considerations of cost, nature of the end product, the effect
desired on the finished product and the particular fragrance sought.
The derivatives of this invention can be used alone or in a perfume
composition as an olfactory component in detergents and soaps; space
odorants and deodorants; perfumes; colognes; toilet waters; bath
preparations such as bath oil and bath salts; hair preparations such as
lacquers, brilliantines, pomades, and shampoos; cosmetic preparations such
as creams, deodorants, hand lotions, and sun screens; powders such as
talcs, dusting powders, face powder, and the like. When used as an
olfactory component of a perfumed article, as little as 50 ppm of one or
more of the preferred hexamethylbicyclo-[2.2.2]-octenol derivative will
suffice to impart a floral, woody odor character. Generally, no more than
five percent is required in the perfume composition. All parts,
percentages, proportions, and ratios herein are by weight unless otherwise
indicated.
In addition, the perfume composition or fragrance composition can contain a
vehicle or carrier for the bicyclo-[2.2.2]-octane derivatives alone or
with other ingredients. The vehicle can be a liquid such as alcohol,
glycol, or the like. The carrier can be an absorbent solid such as gum or
components for encapsulating the composition.
Such bicyclo-[2.2.2]-octane derivatives are also useful in flavoring
compositions. Flavoring compositions are herein taken to mean those which
contribute a part of the overall flavor impression by supplementing or
fortifying a natural or artificial flavor in a material, as well as those
which supply substantially all the flavor and/or aroma character to a
consumable article.
The term "foodstuff" as used herein includes both solid and liquid
ingestible materials for man or animals, which materials usually do, but
need not, have nutritional value. Thus, foodstuffs includes meats,
gravies, soups, convenience foods, malt and other alcoholic or
non-alcoholic beverages, milk and diary products, nut butters such as
peanut butter and other spreads, seafoods including fish, crustaceans,
mollusks and the like, candies, breakfast foods, baked goods, vegetables,
cereals, soft drinks, snack foods, dog and cat foods, other veterinary
products, and the like.
The term "tobacco" will be understood herein to mean natural products such
as, for example, burley, Turkish tobacco, Maryland tobacco, flue-cured
tobacco and the like including tobacco-like or tobacco-based products such
as reconstituted or homogenized leaf and the like, as well as tobacco
substitutes intended to replace natural tobacco, such as lettuce and
cabbage leaves and the like. The tobaccos and tobacco products include
those designed or used for smoking such as in cigarette, cigar, and pipe
tobacco, as well as products such as snuff, chewing tobacco, and the like.
When the bicyclo-[2.2.2]-octane derivatives according to this invention are
used in a flavoring composition, they can be combined with conventional
flavoring materials or adjuvants. Such co-ingredients or flavoring
adjuvants are well known in the art for such use and have been extensively
described in the literature. Apart from the requirement that any such
adjuvant material be ingestibly acceptable, and thus non-toxic or
otherwise non-deleterious, conventional materials can be used and broadly
include other flavor materials, vehicles, stabilizers, thickeners, surface
active agents, conditioners, and flavor intensifiers.
Such conventional flavoring material include saturated, unsaturated, fatty
and amino acids; alcohols, including primary and secondary alcohols;
esters, carbonyl compounds, including ketones and aldehydes; lactones;
cyclic organic materials including benzene derivatives, alicyclics,
heterocyclics such as furans, thiazoles, thiazolidines, pyridines,
pyrazines and the like; other sulfur-containing materials including
thiols, sulfides, disulfides and the like; proteins; lipids;
carbohydrates; so-called flavor potentiators such as monosodium glutamate,
guanylates, and inosinates; natural flavoring materials such as cocoa,
vanilla, and caramel; essential oils and extracts such as anise oil, clove
oil, and the like; artificial flavoring materials such as vanillin; and
the like.
It has been found in certain preferred embodiments that various adjuvants
are particularly suited for use with derivatives according to the present
invention. In view of the utility of compounds according to the present
invention for woody, beverage flavors and for enhancing such flavors, it
is preferred in certain embodiments that the bicyclo-[2.2.2]-octane
derivative or derivatives be combined with one or more adjuvants such as
ethyl-2-methylbutyrate, butyl valerate, 2,3-diethyl pyrazine,
benzaldehyde, cyclotene(2-hydroxy-3-methyl-2-cyclopenten-1-one) and/or
vanillin.
Stabilizers include preservatives such as sodium chloride, and the like,
antioxidants such as calcium and sodium ascorbate, ascorbic acid,
butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate and the
like, sequestrants such as citric acid, EDTA, phosphates, and the like.
Thickeners include carriers, binders, protective colloids, suspending
agents, emulsifiers, and the like, such as agar-agar, carrageenan,
cellulose and cellulose derivatives such as carboxymethyl cellulose and
methyl cellulose, and the like, and other proteinaceous materials, lipids,
carbohydrates, starches and pectins.
Surface active agents include emulsifying agents such as mono- and/or
diglycerides of fatty acids including capric acid, caprylic acid, palmitic
acid, myristic acid, oleic acid, and the like, lecithin, defoaming and
flavor-dispersing agents such as sorbitan monostearate, potassium
stearate, hydrogenated tallow alcohol, and the like.
Conditioners include compounds such as bleaching and maturing agents such
as benzoyl peroxide, calcium peroxide, hydrogen peroxide and the like;
starch modifiers such as peracetic acid, sodium chlorite, sodium
hypochlorite, propylene oxide, succinic anhydride and the like, buffers
and neutralizing agents such as sodium acetate, ammonium bicarbonate,
ammonium phosphate, citric acid, lactic acid, vinegar and the like;
colorants such as carminic acid, cochineal, turmeric, curcumin, approved
food and drug dyes, and the like; firming agents such as aluminum sodium
sulfate, calcium chloride and calcium gluconate; texturizers; anti-caking
agents such as aluminum calcium sulfate and tribasic calcium phosphate;
enzymes; yeast foods such as calcium lactate and calcium sulfate; nutrient
supplements such as iron salts including ferric phosphate, ferric
pyrophosphate, ferrous gluconate and the like, riboflavin, vitamins, zinc
sources such as zinc chloride, zinc sulfate, and the like.
The bicyclo-[2.2.2]-octane derivatives, or the compositions incorporating
them, as mentioned above, can be combined with one or more vehicles or
carriers for adding them to the particular product. Vehicles can be edible
or otherwise suitable materials such as ethyl alcohol, propylene glycol,
water, and the like. Carriers include materials such as gum arabic,
carrageenan, other gums, and the like. The compounds according to this
invention can be incorporated with the carriers by conventional means such
as spray-drying, drum-drying, and the like. Such carriers can also include
materials for coacervating the bicyclo-[2.2.2]-octane derivatives (and
other flavoring ingredients, as present) to provide encapsulated products.
When the carrier is an emulsion, the flavoring composition can also
contain emulsifiers such as mono- and diglycerides of fatty acids and the
like. With these carriers or vehicles, the desired physical form of the
composition can be prepared.
It will be understood by those skilled in the art that the
bicyclo-[2.2.2]-octane derivatives according to the present invention can
be added to the materials to be flavored at any convenient point in the
production of the finished product. Thus, when the derivatives are used to
alter or otherwise vary the flavor of the foodstuff, they can be added in
the original mixture, dough, emulsion, batter, syrup, or the like prior to
any cooking or heating operation. Alternatively, they can be added at a
later stage of processing if volatilization losses would be excessive
during the earlier processing.
When the derivatives are used to treat tobacco products for example, the
additive can be applied in a suitable manner, as by spraying, dipping, or
otherwise. They can be applied during the "casing" or final spray
treatment of the tobacco, or they can be applied at some earlier stage of
curing or preparation. The quantity of bicyclo-[2.2.2]-octane derivatives
or mixtures thereof utilized should be sufficient to impart the desired
flavor characteristic to the product, but on the other hand, the use of an
excessive amount of the derivative is not only wasteful and uneconomical,
but in some instances too large a quantity may unbalance the flavor or
other organoleptic properties of the product consumed. The quantity used
will vary depending upon the ultimate foodstuff, tobacco product, or other
consumable product; the amount and type of flavor initially present in the
product; the further process or treatment steps to which the product will
be subjected; regional and other preference factors; the type of storage,
if any, to which the product will be subjected; and the preconsumption
treatment, such as baking, frying, and so on, given to the product by the
ultimate consumer. Accordingly, the terminology "effective amount" and
"sufficient amount " is understood in the context of the present invention
to be quantitatively adequate to alter the flavor of the foodstuff,
tobacco, or other consumable material.
It is accordingly preferred that the ultimate compositions contain from
about 0.1 parts per million (ppm) to about 250 ppm of
bicyclo-[2.2.2]-octane derivative or derivatives. More particularly, in
food compositions it is desirable to use from about 0.5 ppm for enhancing
flavors and in certain preferred embodiments of the invention, from about
1 to 25 ppm of the derivatives are included to add positive flavors to the
finished product. On the other hand, tobacco compositions can contain as
little as 0.5 ppm and as much as 200 ppm depending upon whether a
cigarette tobacco, a pipe tobacco, a cigar tobacco, a chewing tobacco, or
snuff is being prepared.
The amount of bicyclo-[2.2.2]-octane derivative or derivatives to be
utilized in flavoring compositions can be varied over a wide range
depending upon the particular quality to be added to the foodstuff,
tobacco, or other consumable material. Thus, amounts of one or more
derivatives according to the present invention from about 1 ppm up to 80
to 90 percent can be incorporated in such compositions. It is generally
found to be desirable to include from about 5 ppm to about 0.1 percent of
the derivatives in such compositions.
It will thus be apparent that the derivatives according to the present
invention can be utilized to alter the sensory properties, particularly
organoleptic properties such as flavor and/or fragrance of a wide variety
of consumable materials.
The bicyclo-[2.2.2]-octane ring structure is formed by the reaction of a
dienophile with an alkyl-substituted cyclohexa-2,4-dienone having the
formula
##SPC40##
where R.sub.1 and R.sub.4 through R.sub.8 have the meaning given above.
Such cyclohexadienone compounds are known and others which are required to
carry out processes of this invention can be produced by oxidation of
substituted benzene compounds. Such reactions will be apparent to those
skilled in the art from a consideration of the present disclosure.
The dienophiles for reaction with the cyclohexadienone are desirably
unsaturated compounds having the formula R.sub.9 -CH=CH-R.sub.10 or the
formula R.sub.9 -C.tbd.C-R.sub.10, R.sub.9 and R.sub.10 are as stated
herein.
With the former dienophile a bicyclo-[2.2.2]-octa-5-ene will be obtained,
while with the latter dienophile a bicyclo-[2.2.2]-octa-5,7-diene will be
obtained. The substituents represented by R.sub.9 and R.sub.10 are chosen
to provide the desired final bicyclo-octane derivative.
When the bicyclic compound is to be substituted with alkyl materials then
alkylene substances are used. In certain preferred embodiments of the
invention the dienophile is ethylene, propylene, butylene, or isobutylene.
When a carboalkoxy compound is to be prepared, an alkyl acrylate ester is
utilized and when a cyano group is desired acrylonitrile or a derivative
thereof is used.
When it is desired to obtain a bicyclo-[2.2.2]-octadiene, acetylene or a
derivative thereof can be used. Thus, in a preferred embodiment an
alkyl-substituted alkyne derivative, particularly 3-methyl-1-butyne can be
utilized.
The Diels-Alder conditions for the formation of the bicyclo-[2.2.2]-octane
derivative can be varied depending upon the particular cyclohexadienone
and dienophile utilized and upon the other factors herein described.
Stoichiometric quantities of reactants are used, although in certain
embodiments it is desirable to use a moderate excess, up to 25 percent, of
the dienophile.
The tricyclic ring formation can be carried out with just the two
reactants, but it is frequently desirable to utilize a reaction vehicle.
Such a vehicle can function as a solvent for the reactants, to moderate
the course of the reaction, to provide more intimate contact between the
reactants, and to improve control over parameters such as temperature and
pressure. The reaction vehicle should be inert and is desirably one in
which both reactants are soluble. In certain embodiments of the invention
it is desirable to use an aromatic hydrocarbon such as benzene or a
substituted aromatic, particularly an alkyl-substituted benzene such as
toluene, xylene, or the like.
The pressure under which the Diels-Alder reaction is carried out can vary
over a range and is desirably superatmospheric. Pressures of from 150 to
400 psig are desirably used in certain embodiments.
The Diels-Alder reaction can be carried out at temperatures of from about
150.degree.C to about 300.degree.C. Below the aforesaid lower temperature
the reaction proceeds at a very low rate. On the other hand, at
temperatures considerably higher than those preferred, the reaction may
proceed uncontrollably and/or produce a relatively large quantity of
unwanted by-products which lower the yield of desirable materials and
complicate purification of the product. The temperature chosen will thus
depend upon the particular reactants utilized. The preferred temperatures
for use with dienophiles which are liquid at normal temperatures are from
about 190.degree.C to 250.degree.C. The product of the
dienophile-cyclohexadiene reaction can be purified and/or isolated by
conventional methods as hereinafter mentioned.
To obtain the novel alcohols according to the present invention the
polyalkylbicyclo-[2.2.2]-octadienone or -octenone is reacted with an
organometallic compound. When it is desired to obtain an alcohol wherein
R.sub.2 or R.sub.3 is hydrogen and the other is hydroxyl, an alkali metal
hydride is used. A preferred hydride for use in carrying out the present
invention is an alkali metal aluminum hydride, a preferred hydride being
lithium aluminum hydride.
When it is desired that one of R.sub.2 and R.sub.3 is alkyl and the other
is hydroxyl, then a metallo alkyl compound can be used. The metallo alkyl
compound for use herein can be an alkyl Grignard reagent such as alkyl
magnesium halide, where the halide is the chloride, bromide or iodide. The
lower alkyl magnesium chlorides are preferred and methyl magnesium
chloride, ethyl magnesium chloride, propyl magnesium chloride, and butyl
magnesium chloride are especially preferred in certain embodiments.
The organometallic compounds also include lower alkyl alkali metal
compounds when it is desired that one of R.sub.2 and R.sub.3 be alkyl.
Preferred compounds include ethyl and methyl lithium.
The reaction with the metallic compounds is desirably carried out in a
vehicle. Preferred vehicles are polar organic solvents, although aromatic
solvents can also be used. The preferred reaction vehicles are cyclic
ethers such as tetrahydrofuran; cyclic polyethers such as dioxane; linear
ethers such as diethyl ether, and linear polyethers such as Diglyme
diethylene glycol dimethyl ether. The reaction vehicle can also comprise
phosphorus materials such as hexamethyl phosphoramide and the like.
The reaction vehicle, as noted above, can also include aromatic solvents,
particularly monocyclic materials such as benzene, toluene, and the like.
The reaction with the organometallic compound is desirably carried out at
temperatures of from 10.degree.C to about 125.degree.C. The use of
temperatures substantially below this desirable range results in extremely
low reaction rates and the use of temperatures substantially above this
range can result in undesirable by-products and unnecessarily high
pressures. It is accordingly preferred to use temperatures in the range of
from 40.degree.C to 100.degree.C, and in many of the preferred embodiments
temperatures of from 60.degree.C to 100.degree.C are utilized.
The reaction can be carried out under a wide range of presssures, depending
on temperature, reactants, and vehicles, but atmospheric and
super-atmospheric pressures are preferred.
The quantity of organometallic material reacting with the bicyclo-octanone
derivative can be varied over a wide range. It is desirable to use at
least a stoichiometric quantity of organometallic compound, and quantities
up to 250 percent of such theoretical amount can be utilized, that is, a
150 percent excess. In general, it is desirable to use from about 125
percent to about 200 percent of the theoretical amount of organometallic
compound to insure good reaction rate and completeness.
The time required for the reaction will vary depending upon the
temperature, reactants, pressure and the like. Ordinarily, reaction times
of from abut two to about 24 hours are desirable. It will be understood
from the present disclosure that temperatures of 100.degree.C will permit
obtaining good yields of salt corresponding to the alcohol in four hours
with relatively small excesses of organometallic compounds, whereas longer
times of 16 to 20 hours can be required with temperatures of 60.degree.C.
After the reaction with the organometallic compound is completed to the
extent desired, the product is then hydrolyzed by acidification or
basification to obtain the alcohol itself. A base or an acid can be added
to water and then this can be used to wash ahd hydrolyze the salt, the
product of the reaction. Such hydrolysis can be carried out over a wide
range of temperatures from 5.degree.C to about 100.degree.C, and
temperatures of 15.degree.C to about 30.degree.C are preferred. In certain
embodiments of the invention the hydrolysis is carried out with an acidic
medium, such as a saturated ammonium chloride solution.
The saturated ring derivatives are produced by hydrogenation of the
bicyclo-[2.2.2]-octadiene or bicyclo-[2.2.2]-octene derivatives with
gaseous hydrogen. The hydrogenation is desirably carried out at
super-atmospheric pressures of 150 to 600 psig, and preferably from 200 to
400 psig to provide a good reaction rate without substantial production of
unwanted by-products.
The temperature is chosen so as to provide reaction times of about one to
eight hours and preferably two to six hours. Accordingly, the temperatures
utilized are in the range of 80.degree.C to 210.degree.C, and preferably
from 100.degree.C to 160.degree.C.
The hydrogenation is desirably carried out in the presence of an inert
vehicle, desirably a lower aliphatic alcohol. Preferred vehicles are
ethanol, propanol, and isopropanol. The reaction is carried out in the
presence of a catalyst, and the metallic hydrogenation catalysts such as
nickel or precious metals such as platinum and palladium. The metallic
catalyst can be utilized on a carrier, and a 5 percent palladium on carbon
catalyst is utilized in certain preferred embodiments of the present
invention.
The intermediate and/or final products obtained can be purified or isolated
by conventional purification after appropriate washing, neutralizing
and/or drying as appropriate. Thus, such products can be purified and/or
isolated by distillation, steam distillation, vacuum distillation,
extraction, preparative chromatographic techniques, and the like.
The following examples are given to illustrate embodiments of the invention
as it is presently preferred to practice it. It will be understood that
these examples are illustrative, and the invention is not to be considered
as restricted thereto except as indicated in the appended claims.
EXAMPLE I
Preparation of 2,3,4,5,6,6-Hexamethylcyclohexa-2,4-dien-1-one
A three-liter reaction flask is charged with 360 ml of acetic anhydride
cooled to -5.degree.C, and 90 ml of concentrated sulfuric acid is added
slowly while maintaining the temperature of the solution below 0.degree.C.
Thereafter, 84 ml of 30 percent hydrogen peroxide is added at -5.degree.C
during 25 minutes. The resulting white slurry is dissolved in 250 ml of
methylene chloride.
The methylene chloride solution is added dropwise in three minutes at
0.degree.C to a solution of 80 g of hexamethylbenzene, 300 ml of methylene
chloride, 360 ml of acetic acid, and 270 ml of concentrated sulfuric acid.
The mixture is stirred at 0.degree.-5.degree.C for 90 minutes and the
resulting yellow solution is poured into 1500 ml of ice-water.
The aqueous layer is separated and extracted three times with 500 ml
portions of methylene chloride. The combined methylene chloride layer and
extracts are washed twice with one-liter portions of water, once with
one-liter of 5 percent aqueous sodium hydroxide solution, once with
one-liter of saturated ferrous ammonium sulfate solution, and twice more
with water. The methylene chloride solution is dried over magnesium
sulfate and distilled from the filtered solution to give 85 g of a
slightly yellow oil.
Fractional distillation over a twelve-inch Vigreaux column gives 76.0 g of
2,3,4,5,6,6-hexamethylcyclohexa-2,4-dien-1-one boiling at
75.degree.-90.degree.C at 0.5 mm Hg.
The infrared spectrum of 2,3,4,5,6,6-hexamethylcyclohexa-2,4-dien-1-one
shows absorptions at 2880-2980, 1620-1660, 1560-1540 (shoulder), 1450,
1370, 1335, 1285, 1262, 1215, 1100, 1070, 1060, 985, 945, 900, 790, 630,
and 600 cm.sup.-.sup.1.
The nuclear magnetic resonance (NMR) spectrum (CDCl.sub.3) shows a 6H
singlet at 1.14.delta., and a 3H singlet at 2.02.delta.. The mass spectrum
exhibits a molecular ion at m/e (ratio of mass to charge) of 178.
EXAMPLE II
Preparation of 1,3,3,4,5,6-Hexamethylbicyclo-[2.2.2]-oct-5-en-2-one
A solution of 70 g of 2,3,4,5,6,6-hexamethylcyclohexa-2,4-dien-1-one in 300
ml of benzene is placed in a two-liter Parr stirred autoclave and the air
is removed by passing ethylene through the reaction vessel. Ethylene is
charged to obtain a 180 psig (pounds per square inch, gauge) pressure at
room temperature and then heated to 200.degree.C for 2-1/2 hours. The
internal pressure increases to a maximum of 400 psi and drops to 340 psi.
After cooling to room temperature the benzene is distilled under reduced
pressure to give 85 g of a light yellow oil comprising Compound (I).
This material has a woody, pine cone, warm aroma.
The infrared spectrum of the
1,3,3,4,5,6-hexamethylbicyclo-[2.2.2]-oct-5-en-2-one exhibits absorptions
at 2860-2970, 1710, 1470, 1455, 1440, 1380, 1375, 1370, 1355, 1260, 1230,
1205, 1140, 1100, 1062, 1055, 1030, and 1010 cm.sup.-.sup.1. The NMR
spectrum shows singlet methyl signals at 0.88, 0.93, 1.07, and
1.12.delta.. The C-5 and C-6 methyls appear at 1.70 and 1.62.delta.
respectively. The mass spectrum shows a molecular ion at m/e 206.
EXAMPLE III
Preparation of 1,2,3,3,4,5,6-Heptamethylbicyclo-[2.2.2]-oct-5-en-2-ol
A three molar solution (170 ml) of methyl magnesium chloride in
tetrahydrofuran is heated to reflux under nitrogen and a solution of 85 g
of 1,3,3,4,5,6-hexamethylbicyclo-[2.2.2]-oct-5-en-2-one in 250 ml of
tetrahydrofuran is added dropwise over a twenty-minute period and the
reaction mixture is refluxed under nitrogen for an additional two hours.
An extra 50 ml of methyl magnesium chloride in 50 ml of tetrahydrofuran is
added and the reaction mixture refluxed for 12 hours.
The excess Grignard reagent and salts are then hydrolyzed with saturated
ammonium chloride solution, added slowly with ice bath cooling, and the
tetrahydrofuran solution is decanted from the salts. The tetrahydrofuran
is distilled from the product under reduced pressure to yield 75 g of
yellow oil. The crude alcohol is distilled over a 12-inch Goodloe packed
column at a 4:1 reflux ratio, and a product boiling at
80.degree.-87.degree.C at 0.5 mm Hg is collected. Recrystallization of the
solid fractions from hexane provides a white crystalline solid melting at
72.degree.-73.degree.C.
The solid has an excellent woody, camphoraceous odor and is quite similar
to patchouli alcohol.
Gas-liquid chromatographic (GLC) analysis of the recrystallized product
shows the presence of two epimeric alcohols, A (Compounds IIa and IIa')
and B (Compounds IIb and IIb'), in the ratio of 1:12.5.
The infrared spectrum of the major alcohol A exhibits absorptions at 3630,
3520, 2860-3000, 1470, 1440, 1390, 1383, 1379, 1368, 1300, 1190, 1180,
1150, 1118, 1099, 1078, 1059, 1050, 1000, 986, 907, and 798
cm.sup.-.sup.1. In the NMR spectrum of the major component (A) five methyl
(3H) singlets appear at 0.95.delta., 1.27.delta., 1.38.delta.,
1.46.delta., and 1.68.delta.. A methyl singlet (6H) appears at
2.82.delta.. The mass spectrum of A shows a molecular ion at m/e 222.
The infrared spectrum of the minor alcohol component (B) exhibits
absorptions at 3580, 3510, 2860-3000, 1470, 1440, 1390, 1378, 1362, 1316,
1297, 1242, 1210, 1184, 1145, 1119, 1098, 1075, 1060, 1050, 1040, 1030,
1000, 910, 880, 800, 740, 708, 680, 615, and 580 cm.sup.-.sup.1. The NMR
spectrum of the minor component (B) shows methyl singlets (3H) at
0.86.delta., 1.23.delta., 1.46.delta., 1.55.delta., 1.60.delta.,
2.88.delta. , and 2.93.delta.. The mass spectrum shows a molecular ion at
m/e 222.
EXAMPLE IV
Preparation of 1,3,3,5-Tetramethyl-7- and
8-carbomethoxybicyclo-[2.2.2]-oct-5-ene
A two-liter autoclave is charged with 68 g of
1,3,5,5-tetramethylcyclohexa-1,3-diene, 45 g of methyl acrylate, and 100
ml of benzene, and the mixture is heated at 200.degree.C for 9 hours. The
solvent is removed by flash-evaporation under reduced pressure to net 102
g of crude product. Fractional distillation over a three-inch
micro-Vigreaux column yields 34 g of an oil boiling at
76.degree.-145.degree.C at 1.2 mm Hg. Gas-liquid chromatography shows the
presence of four components: major component B (Compound III) and three
minor components A, C, and D (Compound IV). The mixture has a green,
minty, valerian aroma.
The infrared spectrum of the major component B exhibits absorptions at:
3025, 2920, 2870, 1870, 1700, 1460, 1450, 1440, 1430, 1375, 1360, 1340,
1320, 1285, 1270, 1250, 1215, 1197, 1160, 1130, 1105, 1020, 990, 980, 920,
800, and 740 cm.sup.-.sup.1.
The NMR spectrum of the major component B shows 3H singlets at 0.78, 0.98,
1.02, 2.00, and 3.56.delta.; and a 1H singlet at 5.38.delta..
The infrared spectrum of component C exhibits absorptions at: 2950, 2860,
1735, 1440, 1360, 1250, 1200, 1170, 1155, 1060, 1020, 1000, 880, and 830
cm.sup.-.sup.1.
The nuclear magnetic resonance spectrum of component C shows 3H singlets at
0.92, 1.74, and 3.64.delta.; and 1H singlets at 5.02 and 5.48.delta..
The infrared spectrum of component D exhibits absorptions at 3070, 2950,
1735, 1650, 1605, 1430, 1360, 1310, 1275, 1240, 1215, 1190, 1140, 1130,
1060, 1040, 1010, 990, 940, 880, 850, 810, 640, and 570 cm.sup.-.sup.1.
The nuclear magnetic resonance spectrum of component D shows 3H singlets at
0.82, 0.92, 0.98, 1.69, and 3.62.delta.; a 2H doublet at 4.67.delta.; and
a 1H singlet at 5.76.delta..
The mass spectrum of the major component B exhibits a molecular ion at m/e
222, as does component D.
The mass spectrum of the component(s) C shows species with as high an m/e
as 236 and 238. Thus, component C is probably a mixture of components of
uncertain molecular weights.
EXAMPLE V
Preparation of 1,3,3,5-Tetramethyl-7-carbomethoxy-bicyclo-[2.2.2]-octane
and 1,3,3,5-Tetramethyl-8-carbomethoxybicyclo-[2.2.2]-octane
A two-liter autoclave is charged with 3.0 g of a mixture of
1,3,3,5-tetramethyl-7 and 8-carbomethoxybicyclo-[2.2.2]-oct-5-ene, 200 ml
of isopropyl alcohol, and 0.05 g of 5 percent palladium on carbon catalyst
and purged with hydrogen gas and then pressurized to 200 psig. The
reaction vessel is heated to 100.degree.C (200 psig) for six and one-half
hours and then allowed to stand until cooled to room temperature.
The catalyst is filtered from the solution, and the solvent removed by
flash evaporation under reduced pressure to net 3.0 g of crude product.
GLC shows two significant peaks which are trapped for spectral data and
odor evaluation. The spectral data indicate that these two components are
most likely conformational isomers. The fragrances of these components are
fruity, green, minty, fig-like, and woody.
The infrared spectrum of the major component A (Compound V) exhibits
absorptions at: 2980-2860, 1725, 1460, 1430, 1360, 1340, 1320, 1280, 1260,
1240, 1210, 1190, 1160, 1130, 1115, 1085, 1060, 1035, 1020, 995, 978, 930,
912, 890 820, 812, 780, and 740 cm.sup.-.sup.1.
The NMR spectrum of the major component A shows 3H singlets at 0.70, 1.05,
and 3.59.delta.; a 6H singlet at 0.96.delta. and a 3H doublet at
1.01.delta.. The mass spectrum exhibits a molecular ion at m/e 224.
The infrared spectrum of the minor component(s) B exhibits absorptions at:
2960-2860, 1730, 1455, 1430, 1380, 1360, 1318, 1262, 1255, 1235, 1210,
1200, 1190, 1160, 1070, 1050, 1020, 1005, 915, 900, 830, 800, 780, and 740
cm.sup.-.sup.1. The NMR spectrum indicates that this trapped sample is
actually a mixture of two isomers. Methyl signals are found at: 0.73,
0.77, 0.92, 1.03, 1.05, and 1.13.delta.. A 3H singlet at 3.59.delta.
accounts for the ester methyl. The mass spectrum of this trapping is very
close to that for the component A. The molecular ion of Compounds VI and V
appears at m/e 224.
EXAMPLE VI
Preparation of 1,3,3,5-Tetramethyl-7 and 8-cyanobicyclo-[2.2.2]-oct-5-ene
A two-liter autoclave is charged with 136 g of 1,3,5,5
-tetramethylcyclohexa-1,3-diene, 53 g of acrylonitrile, and 500 ml of
benzene and heated to 200.degree.C for 6 hours and then allowed to cool to
room temperature. The solvent is flash-evaporated under reduced pressure
to net 176.4 g of crude product. Gas-liquid chromatography shows the
presence of two major peaks and a small amount of starting material. The
crude oil is rushed over a two-inch splash column to yield 139 g boiling
71.degree.-75.degree.C at 0.3 mm Hg. The fragrances of these components
are woody, camphoraceous, minty, and floral.
The infrared spectrum of component(s) A (Compound VII) shows absorptions
at: 3010, 2960, 2920, 2860, 2230, 1650, 1450, 1380, 1365, 1335, 1315,
1282, 1210, 1190, 1150, 1130, 1040, 1022, 1003, 965, 910, 802, 715, and
660 cm.sup.-.sup.1. The NMR spectrum of component A exhibits 3H singlets
at 0.80, 1.12, 1.18, and 1.76.delta.. The 1H singlet (vinyl proton) is
found at 5.42.delta.. The mass spectrum shows a molecular ion at m/e 189.
The infrared spectrum of components B (Compound VIII) shows absorptions at
3010, 2960, 2910, 2235, 1455, 1450, 1380, 1360, 1340, 1210, 1190, 1160,
1020, 980, 975, 800, and 795 cm.sup.-.sup.1. The NMR spectrum of the
component designated as B shows that it is probably a mixture of isomers,
since there are an excessive number of methyl group signals. There are
four methyl signals that integrate for a total of 9 protons or 3 methyl
groups at: 0.79, 0.97, 1.10, and 1.23.delta. when a fifth methyl signal at
1.81.delta. is taken as three protons and a vinyl proton signal at
5.48.delta. is taken as one proton. The mass spectrum is very similar to
that of component A in that a molecular ion is again noted at m/e 189.
EXAMPLE VII
Preparation of 1,3,3,5-Tetramethyl-7 and 8-cyanobicyclo-[2.2.2]-octane
A two-liter autoclave is charged with 15.0 g | | |
