Novel .alpha.-hydroxyalkyl-4-t-alkylcyclohexanes possessing a sandalwood note, their utility as olfactory agents, and perfume compositions containing them.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
Novel carbocyclic odorants. 
2. The Prior Art 
According to Guenther (E. Guenther, "The Essential Oils", Vol. V, page 173, 
D. Van Nostrand Co., Inc., New York (1952), East Indian Sandalwood Oil 
"has been perhaps one of the most precious perfumery materials from 
antiquity down to modern times, and its popularity has shown no signs of 
waning." 
As with many other natural materials which contribute highly desirable 
nuances to perfume compositions, East Indian Sandalwood Oil is subject to 
the vagaries of natural products. Perfumers are necessarily restricted in 
the use of this valuable ingredient because of its high cost and limited 
supply. 
The major constituents of sandalwood oil, .alpha.- and .beta.-santalol, are 
known to be mainly responsible for its desired odor. There is, however, no 
commercially feasible process for the synthesis of these compounds. 
Accordingly, there is a continuing effort to provide synthetic materials 
which possess a sandalwood odor. Consequently, any substances possessing a 
sandalwood odor which are economical, and can be made readily available, 
will find immediate and appreciable commercial interest as a replacement 
or partial replacement for natural sandalwood oil in fragrance 
compositions. 
SUMMARY OF THE INVENTION 
In accordance with the present invention there is provided novel 
.alpha.-hydroxyalkyl-4-t-alkylcyclohexanes and perfume compositions 
containing same. The novel compounds of this invention can be represented 
by the general formula: 
##STR1## 
wherein R.sub.1 represents an alkyl group of from one to three carbons and 
R.sub.2 represents a tertiary alkyl group wherein the tertiary carbon is 
bonded to the cyclohexane ring. The compounds are further defined by 
requiring that the total number of carbons in R.sub.1 +R.sub.2 not exceed 
ten. It should also be understood that R.sub.2, the tertiary alkyl group, 
shall include both aliphatic t-alkyl groups and alicyclic t-alkyl groups. 
It is the surprising and unexpected finding that the novel secondary 
alcohols of this invention possess the fine, precious, woody notes 
reminiscent of sandalwood oil. These compounds have simple monocyclic 
structures which are totally unrelated to the more complex structures of 
.alpha.-and .beta.-santalol. It is also surprising that while the 
secondary alcohols of this invention all possess the sandalwood notes 
(differing from one another only in degree) the corresponding primary and 
tertiary alcohols are devoid of sandalwood notes. Similarly, the 
corresponding secondary alcohols wherein R.sub.2 was not a tertiary alkyl 
group, lacked the fine sandalwood quality of the claimed compounds. 
The compounds of this invention can be prepared in a variety of ways. The 
method which might be preferred in each case will normally be determined 
by the cost and availability of the required starting material. In 
general, the compounds can be prepared from appropriate t-alkylbenzenes or 
4-t-alkylcyclohexanones by a variety of methods, some of which are 
indicated in Chart I. 
##STR2## 
In path A of Chart I, the t-alkylbenzene is alkanoylated via a Friedel 
Crafts type alkanoylation to provide a composition consisting essentially 
of the desired 4-t-alkylalkanoylbenzene. The ketone prepared is then 
hydrogenated in the presence of a suitable catalyst to provide the desired 
alcohol I. 
In path B of Chart I, the 4-t-alkylcyclohexanone is reacted with the 
appropriate metal acetylide to provide the ethynyl alcohol which is 
converted to the appropriate alkanoylcyclohexene via the known Rupe 
rearrangement. The 4-t-alkyl-1-alkanoylcyclohexene is then reduced in 
either one or two steps to provide the desired alcohol I. 
Path C illustrates a method by which the 4-t-alkylcyclohexanone is 
converted to the 4-t-alkylcyclohexene by reducing first to the alcohol and 
then dehydrating to provide the olefin. The olefin is then converted to a 
composition comprising the 4-t-alkyl-1-alkanoylcyclohexene via the known 
Kondakov reaction, the product then being converted to the desired alcohol 
I as previously indicated. 
Path D illustrates another alternative which utilizes the well known 
Darzen's reaction to convert the 4-t-alkylcyclohexanone to the aldehyde 
(R.sub.4 =H) when esters of chloroacetic acid are used, or to ketones 
(R.sub.4 .noteq.H) when esters of higher .alpha.-chloroacids are used. 
Ketones so produced can be converted to the desired alcohol I by an 
appropriate reduction of the carbonyl group. Aldehyde products of the 
Darzen's reaction can be converted to the desired alcohol I by reacting 
the aldehyde with an appropriate organometallic derivative such as an 
alkyl lithium reagent or Grignard reagent. 
The compounds of the present invention fluid use as odorants and may be 
used in perfumes, soaps and other toilet goods. They are especially, 
though not exclusively, useful as replacements or partial replacements for 
natural sandalwood oil. 
DESCRIPTION OF THE PREFERRED EMBODIMENTS 
As indicated previously, the alcohols of this invention can be prepared in 
several ways. Some of the 1-alkanoyl-4-t-alkylbenzene, 
1-alkanoyl-4-t-alkylcyclohexene and 4-t-alkylcyclohexylcarboxaldehyde 
(1-formyl-4-t-alkylcyclohexane) derivatives required as intermediates in 
this invention are known in the prior art or can be prepared by utilizing 
chemical reactions well known in the art such as those illustrated in 
Chart I. For example: 1-acetyl-4-t-butylcyclohexene has been reported by 
M. S. Newman et al., J. Am. Chem. Soc. 82, 4098 (1960); 
1-formyl-4-t-butylcyclohexane has been reported by B. Cross et al., J. 
Chem. Soc., 3895 (1960); and 4-t-butylacetophenone has been reported by J. 
C. Butler et al., J. Am. Chem. Soc., 76, 1906 (1954). 
In method A of Chart I it is preferred to reduce the 
1-alkanoyl-4-t-alkylbenzene compounds to the desired alcohol I using 
either a rhodium or ruthenium catalyst in order to minimize 
hydrogenolysis. 
Requirements regarding the amount of catalyst, solvent, reaction 
temperature, hydrogen pressure and reaction time (though probably not 
independent of one another) do not seem to be critical. It is preferred to 
use a 5% Rh/C or 5% Rh/alumina catalyst in amounts ranging from 0.5 to 10% 
by weight of the ketone charged. The hydrogenation is suitably carried out 
at temperatures between 25.degree. C. and 60.degree. C. and at pressures 
between 30 psi and 300 psi. 
The use of a solvent is optional. The hydrogenation can be affected without 
a solvent or in a suitable inert solvent such as ethanol, acetic acid, 
pentane etc. The amounts of catalyst mentioned, the temperatures and 
pressures given as well as the solvents used are intented to illustrate, 
but not limit this invention. 
Alternatively, the hydrogenation of this ketone can be accomplished in two 
steps by first reducing the carbonyl group to an alcohol by methods known 
in the art (e.g. NaBH.sub.4, LiAlH.sub.4, normal catalytic reduction etc.) 
followed by hydrogenation of the resulting benzylic alcohol using rhodium 
catalyst as previously described. 
In accordance with methods B and C of Chart I, the 
1-alkanoyl-4-t-alkylcyclohexene can be hydrogenated to the novel alcohol I 
by a number of methods known in the hydrogenation art for hydrogenating 
.alpha.,.beta.-unsaturated ketones to saturated alcohols. A two-step 
process can be utilized in which one of the unsaturated moieties is 
reduced before the other. It is preferred, however, to reduce the 
1-alkanoyl-4-t-alkylcyclohexene by hydrogenating both the olefin and the 
carbonyl in a single step process. 
Requirements for the single step process regarding the amount of catalyst, 
solvent, reaction temperature, hydrogen pressure and reaction time (though 
probably not independent of one another) do not seem to be critical. A 
number of catalysts are known in the art to convert .alpha., 
.beta.-unsaturated ketones to saturated alcohols, e.g., Platinum, 
Palladium, Raney Nickel, Rhodium, Ruthenium. 
We prefer to use the economical Raney Nickel since it was unexpectedly 
found that this catalyst produces a product in which the cis isomer 
predominates. Here again, conditions do not seem to be critical regarding 
temperature, solvent pressure, and amount of catalyst. (Separation of 
1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane into its cis and trans 
isomers revealed that the desirable sandalwood odorant properties of this 
compound are due predominantly to the cis isomer). 
The preferred amount of catalyst is between 5-15% of the amount of ketone 
charged. The preferred temperature range is between 80.degree. C. and 
120.degree. C. and the preferred pressure range is from 60 psi to 600 psi. 
Solvents may be used but are not necessary as the hydrogenation proceeds 
in the absence of solvent. If solvents are used, the preferred ones are 
those having a low vapor pressure under the hydrogenation conditions. Such 
a list of temperature ranges, pressure ranges and catalyst amounts is 
given to illustrate preferred reaction conditions and is not intended to 
limit this invention. Conditions well outside the ranges given would be 
applicable in most cases. The fact that the product formed was enriched in 
the cis isomer when Raney Nickel was used as catalyst, was quite 
unexpected. A 1:1 mixture was expected as was found in the other methods 
tried. 
In comparison, when Raney Nickel was used, the 
.alpha.-hydroxyalkyl-4-t-alkylcyclohexane produced was enriched in the cis 
isomer, the cis to trans isomer ratio being in the range of about 2-3 to 
1. 
In accordance with Method D, the 4-t-alkylcyclohexylcarboxaldehyde can be 
brought to reaction with the suitable metal alkyl R.sub.1 M by utilizing a 
number of procedures known in the art. It is preferred to effect reaction 
by adding the aldehyde over a period of time to a solution of the metal 
alkyl in an appropriate reaction inert solvent and, upon completion of 
reaction, to decompose the initial adduct with a protonic source such as 
an acid. 
The metal alkyl is suitably a Grignard reagent (e.g., R.sub.1 MgX wherein X 
is Cl, Br or I) or lithium alkyl (e.g., R.sub.1 Li) all of which are 
commercially available or can be prepared by methods known in the art. 
The solvent is preferably an ether such as ethyl ether, THF, etc., or an 
ether-hydrocarbon mixture such as ethyl ether-toluene, THF-toluene, 
THF-benzene etc. Such procedures are well known to those skilled in the 
art. 
As mentioned, the compounds of this invention can be represented by the 
formula: 
##STR3## 
The essential features of R.sub.1 and R.sub.2 are that R.sub.1 be a lower 
alkyl (not hydrogen) and that R.sub.2 be a tertiary alkyl group wherein 
the tertiary alkyl carbon is attached to the cyclohexyl ring. 
A finding of this invention is that compounds having the aforementioned 
structural features share in common an odoriferous note reminiscent of 
sandalwood. Compounds which do not have these essential features, i.e., if 
the alcohol is a primary or tertiary alcohol or the R.sub.2 group is not 
tertiary alkyl, do not share the property of having a sandalwood odor. 
Present data indicate that R.sub.1 can be a lower alkyl from one to three 
carbon atoms and that R.sub.2 can be a tertiary alkyl from four to eight 
carbon atoms. Initially it was believed that the lower molecular weight 
analog, the 1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane, had the more 
intense odor and was preferred. This view was reinforced as being 
consistent with the idea that the lower molecular weight compound would be 
more volatile and therefore probably more intense. Further testing has 
shown, surprisingly, that certain higher homologs are preferred. The final 
preference of one analog over another is most probably in the hands of the 
perfumer who will decide based on personal preference and/or the special 
requirements of the formulation he is creating. 
Certain general tendencies do, however, seem to appear upon a comparison of 
the compounds. As one increases the bulk of the .alpha.-hydroxyethyl group 
from two to four carbons, the odor intensity seems to diminish with each 
carbon added. Therefore, it is especially preferred that R.sub.1 be methyl 
as opposed to ethyl or propyl in those cases where odor intensity is 
important. 
Changes in R.sub.2 are less pronounced and seem unpredictable. While the 
simplest analog (R.sub.2 =t-butyl) has a fine intense sandalwood odor, a 
number of the higher homologs are preferred by some perfumers. Those 
analogs having R.sub.2 as a five or six carbon moiety have fine intense 
sandalwood odors, perhaps stronger than the t-butyl analog. Those wherein 
R.sub.2 is a seven carbon group seem less intense than the six carbon 
analogs, but still have fine sandalwood odors. Based on present 
observations, the sum of R.sub.2 +R.sub.1 should not exceed ten carbon 
atoms. Thus, the preferred secondary alcohols of this invention would 
range between 12 and 17 carbon atoms, with 12 to 15 carbon atom alcohols 
having R.sub.1 as methyl being especially preferred. 
Separation of 1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane into its cis 
and trans isomers revealed that the desirable sandalwood odorant 
properties of that composition were due predominantly to the cis isomer. 
While this may create a presumption that the cis isomer of the higher 
homologs would be preferred, such data was not obtained since there is no 
commercially practical way to separate the isomers and since the mixture 
is a fine odorant in itself. (The pure 
cis-1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane appears to have little 
advantage, if any, over the mixture of isomers). 
When blended with the aromatic oils, concentrates and chemicals used in the 
perfume arts, the novel .alpha.-hydroxyalkyl-4-t-alkylcyclohexanes of this 
invention impart natural sandalwood notes to such formulations. They are 
particularly useful for their use in formulations to replace or extend 
natural sandalwood oil. 
For the most part, the aroma chemicals herein evaluated can be used in 
perfume formulations in a practical range extending from 0.1 to 30 
percent. This will vary, of course, depending upon the type of fragrance 
formula involved. Concentrations above 30 percent, even as high as 80 or 
90 percent, may be used successfully for special effects. 
The compounds can be used to prepare odorant compositions which can be used 
as odorant bases for the preparation of perfumes and toilet waters by 
adding the usual alcoholic and aqueous diluents thereto: approximately 
15-20% by weight of base would be used for the former and approximately 
3-5% by weight would be used for the latter. 
Similarly, the base compositions can be used to odorize soaps, detergents, 
cosmetics, or the like. In these instances, a base concentration of from 
about 0.5 to about 2% by weight can be used.

The following examples are provided to illustrate further the practice of 
the present invention, but are for purposes of preferred embodiments only 
and should not be construed as limiting. 
Unless otherwise indicated, temperatures are in .degree. C., infrared bands 
are reported in inverse centimeters, nuclear magnetic resonance spectra 
were run in chloroform-d.sub.1 and signals are reported in .delta. units 
relative to TMS (.delta.0.0), and molecular weights were determined by 
mass spectroscopy. Gas-liquid chromatography was also used to analyze the 
products. 
EXAMPLE I 
This example provides a general procedure to prepare the compounds of this 
invention according to path B of Chart I. 
A. Preparation of t-alkylcyclohexanones 
The procedure for preparing the 4-(3-methylpent-3-yl)cyclohexanone is 
offered for illustration. The other t-alkylcyclohexanones can be similarly 
prepared. 
1. Preparation of 4-(3-methylpent-3-yl)cyclohexanone 
(a) Preparation of 4-(3-methylpent-3-yl)phenol 
A mixture of phenol (396 g, 4.2 mol), 3-methyl-3-pentanol (230 g. 2.25 
mol), 85% phosphoric acid (50 g, 0.43 mol) and benzene (1.5 liters) was 
refluxed and the azeotroped water was collected in a Dean Stark trap (53 
ml). The reaction mixture was cooled and transferred to a separatory 
funnel. A small bottom layer was separated and the top (organic) layer was 
washed with 500 ml portions of water until the pH of the washes was 7 
(neutral). The solvent was removed on a rotary evaporator. Distillation of 
the residual oil under vacuum gave the desired 
4-(3-methylpent-3-yl)phenol: 365 g, 91% yield; bp 112.degree. C. (1.0 mm); 
mol wt. 178 (ms); nmr, 0.68 (6H, t, J=8 2-methyls), 1.26 (3H, s, methyl), 
1.4-2.0 (4H, m, --CH.sub.2 --), 6.28 (1H, s, hydroxyl), 6.8-7.3 (4H, m, 
aromatics); ir, 3260, 2980, 2940, 2890, 1615, 1600, 1515, 1466, 1380, 
1250, 1190, 1120, 830 cm.sup.-1. 
(b) Preparation of 4-(3-methylpent-3-yl)cyclohexanol 
A mixture of the 4-(3-methylpent-3-yl)phenol (365 g, 2.05 mol), ethanol 
(600 g), acetic acid (5.0 g) and 5% rhodium on carbon (8.0 g) was 
hydrogenated at 100 psi and 60.degree. C. until the hydrogen absorption 
essentially ceased. The reaction mixture was filtered to remove the 
catalyst and the solvent was removed on a rotary evaporator. The resulting 
oil was washed with 10% sodium bicarbonate (200 ml) and then with water 
(200 ml portions) until a neutral pH (7) was indicated. Distillation of 
the crude oil under vacuum gave the desired 
4-(3-methylpent-3-yl)cyclohexanol: 350 g, 93% yield; bp 
110.degree.-115.degree. C. (2.0 mm); mol wt 184 (ms); nmr, 0.4-0.9 (9H, 
methyls), 1.0-1.5 (14H, m, CH.sub.2), 2.39 (1H, s, hydroxyl), 4.0 (1H, m, 
H.alpha. to oxygen); ir, 3350, 2980, 2950, 2890, 1455, 1385, 1075, 1046, 
960 cm.sup.-1. 
(c) Preparation of 4-(3-methylpent-3-yl)cyclohexanone 
The 4-(3-methylpent-3-yl)cyclohexanol (350 g, 1.9 mol) prepared above was 
added slowly over a 3 hour period to a stirring solution of sodium 
dichromate (614 g, 2.06 mol), water (3.0 liters) and 98% sulfuric acid 
(526 g) while maintaining the batch temperature at 50.degree.-55.degree. 
C. Upon completion of the addition, the mixture was stirred an additional 
hour at 50.degree. C. The reaction mixture was cooled and three liters of 
benzene was added. The layers were separated and the organic layer washed 
with one liter portions of water until a neutral pH was indicated. The 
solvent was removed on a rotary evaporator. Distillation of the residual 
oil under vacuum gave the desired 4-(3-methylpent-3-yl)cyclohexanone: 274 
g, 79% theory; bp 105.degree. C. (0.5 mm); mol wt 182 (ms); nmr, 0.75 (3H, 
s, methyl, 0.8 (6H, t, J=7, methyls), 1.15-2.0 (9H, m, CH, CH.sub.2), 
2.15-2.5 (4H, m, H.alpha. to carbonyl); ir, 2980, 2890, 1720, 1465, 1390, 
1170 cm.sup.-1. 
2. In a like manner, other t-alkylcyclohexanones of this invention can be 
prepared by utilizing the appropriate tertiary alcohol in the above 
procedure. Among those prepared were: 
(a) 4-(2-methylpent-2yl)cyclohexanone bp 88.degree.-90.degree. C. (1.0 mm) 
(b) 4-(3-ethylpent-3-yl)cyclohexanone bp 79.degree.-80.degree. C. (0.3 mm) 
(c) 4-(1-methylcyclopentyl)cyclohexanone bp 110.degree. C. (0.5 mm) 
(d) 4-(1-methylcyclohexyl)cyclohexanone mp 47.degree.-8.degree. C. (solid) 
All of the above compounds had ir, nmr and ms spectra consistent with their 
structure. 
B. Preparation of 1-acetyl-4-t-alkylcyclohexenes 
The procedure for preparing 1-acetyl-4-t-amylcyclohexene is offered for 
illustration. The other 1-acetyl-4-t-alkylcyclohexenes can be prepared 
similarly. 
1. Acetyl-4-t-amylcyclohexene 
To a stirred mixture of 46 g of lithium acetylide in 200 ml of benzene was 
added, 84.0 g (0.5 mol) of 4-t-amylcyclohexanone over a period of 3 hr. 
The mixture was stirred for an additional hour. Water (500 ml) was then 
added dropwise and the mixture was refluxed for 1 hr. The mixture was 
allowed to cool and was separated. The aqueous phase was extracted with 
ether. The combined organic phase was washed with water, dried over 
magnesium sulfate, filtered, and concentrated under reduced pressure. 
Distillation of the residual oil gave cis and 
trans-4-t-amyl-1-ethynylcyclohexanol: 49.8 g, 51% yield, bp 
103.degree.-104.degree. (0.5-1.0 mm); nmr, 2.48 (1H, s, ethynyl H), 0.78 
(9H, methyl H); ir, 3380, 3300, 1064 cm.sup.-1. 
A solution of 24.0 g (0.12 mol) of cis and 
trans-4-t-amyl-1-ethynylcyclohexanol and 75 ml of 90% formic acid was 
heated under reflux for 2 hr. The solution was allowed to cool. Excess 10% 
sodium hydroxide solution was added dropwise and the mixture extracted 
with ether. The etherial extract was washed with water, dried over 
magnesium sulfate, filtered, and concentrated under reduced pressure. 
Distillation of the residual oil gave 1-acetyl-4-t-amylcyclohexene: 13.2 
g, 55% yield; bp 63.degree.-64.degree. (0.1 mm); mol wt 194 (ms); nmr, 
6.93 (1H, broad, vinylic H), 2.25 (3H, s, acetyl methyl), 0.82 (9H, methyl 
H); ir, 1662, 1639, 1385, 1248, 1068, 964, 907 cm.sup.-1. 
2. In a like manner, other 1-acetyl-4-t-alkylcyclohexenes of this invention 
can be prepared by utilizing the appropriate ketone in the above 
procedure. Among those prepared were: 
(a) 1-Acetyl-4-(3-methylpent-3-yl)cyclohexene bp 84.degree.-6.degree. 
C.(0.15 mm) 
(b) 1-Acetyl-4-(2-methylpent-2-yl)cyclohexene bp 82.degree.-4.degree. 
C.(0.15 mm) 
(c) 1-Acetyl-4-(3-ethylpent-3-yl)cyclohexene bp 95.degree.-100.degree. 
C.(1.0 mm) 
(d) 1-Acetyl-4-(1-methylcyclopentyl)cyclohexene bp 88.degree.-90.degree. C. 
(0.3 mm) 
(e) 1-Acetyl-4-(1-methylcyclohexyl)cyclohexene bp 92.degree.-100.degree. C. 
(0.15 mm) 
All the above compounds had ir, nmr and ms spectra consistent with their 
structure. 
C. Preparation of 1-(.alpha.-hydroxyethyl)-4-t-alkylcyclohexanes from the 
1-acetyl-4-t-alkylcyclohexenes. 
The procedure for preparing the 
1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane is offered for illustration. 
The other 1(.alpha.-hydroxyethyl)-4-t-alkylcyclohexenes can be similarly 
prepared. 
1. 1-(.alpha.-Hydroxyethyl)-4-t-Butylcyclohexane from 
1-acetyl-4-t-butylcyclohexene 
(a) Two Step Process 
A solution of 70 g (0.39 mol) of 1-acetyl-4-t-butylcyclohexene in 200 ml 
ethanol was hydrogenated with 0.5 g of 5% palladium on charcoal on a Parr 
hydrogenation apparatus under 50 psi hydrogen pressure. When the 
theoretical amount (0.39 mol) of hydrogen was absorbed, the reaction was 
stopped, the mixture filtered, concentrated, and distilled under reduced 
pressure to give ca. 1:1 mixture of cis and 
trans-1-acetyl-4-t-butylcyclohexane: 64.6 g, 91% yield; bp 
64.degree.-92.degree. C. (8 mm); mol wt. 182 (ms); nmr shows no vinylic 
hydrogen. 
A solution of 30 g (0.16 mol) of this 1:1 mixture of cis and 
trans-1-acetyl-4-t-butylcyclohexane in 30 ml anhydrous ether was added 
dropwise to a stirred mixture of 4 g lithium aluminum hydride in 200 ml 
anhydrous ether. After addition, the mixture was heated under reflux for 5 
hours, allowed to cool, and saturated ammonium chloride solution was added 
dropwise until a clear ether layer was obtained. The mixture was filtered, 
washed with 10% sodium hydroxide solution, washed with water, dried, 
concentrated, and distilled to give a 1:1 mixture of cis and 
trans-1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane: 25.0 g, 83.3% yield; 
bp 75.degree.-85.degree. C. (2 mm); mol wt 184; nmr, no absorption between 
2.0-2.2 (acetyl methyl H); ir 3330 (hydroxyl). 
(b) Single Step Process with Raney Nickel in Solvent 
A mixture of 353 g (2.0 mol) of 1-acethyl-4-t-butylcyclohexene, 100 ml of 
n-butanol, and 35 g of Raney Nickel (activated by repeated washing with 
methanol) was hydrogenated at 100.degree. with 300 psi hydrogen pressure 
until hydrogen uptake essentially stopped (3.1 moles hydrogen consumed, 
78% of the theoretical amount). The catalyst was removed by filtration, 
replaced with fresh catalyst, and the reaction resumed until the remaining 
0.9 mole of hydrogen was consumed. After filtration and removal of 
solvent, the crude product 1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane 
consisted of 77% of the cis isomer and 23% of the trans isomer. 
(c) Single Step Process with Raney Nickel without Solvent 
A mixture of 200 g (1.11 mol) of 1-acetyl-4-t-butylcyclohexene and 20 g of 
Raney Nickel (activated by repeated washing with methanol) was 
hydrogenated at 100.degree. with 300 psi hydrogen pressure until hydrogen 
uptake ceased (2.2 moles hydrogen consumed). After filtration, the crude 
product 1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane consisted of 64% of 
the cis isomer and 36% of the trans isomer, uncontaminated with any 
1-acetyl-4-t-butylcyclohexane. 
2. In a like manner, other 1-(.alpha.-hydroxyethyl)-4-t-alkylcyclohexanes 
of this invention can be prepared by utilizing the proper 
1-acetyl-4-t-alkylcyclohexene in the above procedures. Among those 
prepared were: 
(a) 1-(.alpha.-Hydroxyethyl)-4-(2-methylbut-2-yl)cyclohexane, also known as 
1-(.alpha.-hydroxyethyl)-4-t-amylcyclohexane; bp 89-94 (1 mm); mol wt 198 
(ms); nmr, 1.20 (0.5H, d, J=6 Hz, methyl .alpha. to OH in cis isomer), 
1.15 (0.5H, d, J=6 Hz, methyl .alpha. to OH in trans isomer), 0.77 (9H, 
sharp, methyl H); ir, 3360, 1455, 1070, 935 cm.sup.-1. 
(b) 1-(.alpha.-Hydroxyethyl)-4-(2-methylpent-2-yl)cyclohexane; bp 95-100 (1 
mm); mol wt 212 (ms); nmr 0.75 (s, methyls) 0.8-1.9 (m, --CH.sub.2, CH, 
methyl .alpha. to oxygen), 2.08 (1H, s, hydroxyl), 3.43 (m, H.alpha. to 
oxygen cis-isomer), 3.86 (m, H.alpha. to oxygen trans-isomer); ir, 3380, 
2980, 2940, 2880, 1475, 1455, 1390, 1370, 1070, 940 cm.sup.-1. 
(c) 1-(.alpha.-Hydroxyethyl)-4-(3-methylpent-3-yl)cyclohexane; bp 82-83 
(0.15 mm); mol wt 212 (ms); nmr 0.66 (3H, s, methyl) 0.71 (6H, t, J=7, 
methyls), 1.05-1.85 (14H, m, CH.sub.2, CH), 1.96 (1H, s, hydroxyl), 3.46 
(q, J=7, H.alpha. to oxygen in cis isomer) 3.88 (m, H.alpha. to oxygen, 
trans-isomer); ir, 3360, 2980, 2940, 2890, 2880, 1460, 1385, 940 
cm.sup.-1. 
(d) 1-(.alpha.-Hydroxyethyl)-4-(3-ethylpent-3-yl)cyclohexane; bp 120-130 
(0.5 mm); mol wt 226 (ms); nmr, 0.7-0.95 (m, methyls), 1.0-1.9 (m, 
CH.sub.2, CH, methyl .alpha. to hydroxyl), 1.9 (1H, s, hydroxyl), 3.5 (m, 
H.alpha. to hydroxy cis-isomer), 3.9 (m, H.alpha. to hydroxyl 
trans-isomer); ir, 3350, 2980, 2940, 2890, 1655, 1380, 1075, 940 
cm.sup.-1. 
(e) 1-(.alpha.-Hydroxyethyl)-4-(1-methylcyclopentyl)cyclohexane; bp 114-120 
(0.5 mm); mol wt 210 (ms); nmr, 0.81 (3H, s, methyl on cyclopentyl), 
1.0-1.8 (m, CH.sub.2, CH, methyl .alpha. to hydroxyl), 1.71 (1H, s, 
hydroxyl), 3.5 (m, H.alpha. to hydroxyl cis-isomer), 3.9 (m, H.alpha. to 
hydroxyl trans-isomer); ir, 3360, 2950, 2870, 1455, 1380, 1070, 940 
cm.sup.-1. 
(f) 1-(.alpha.-Hydroxyethyl)-4-(1-methylcyclohexyl)cyclohexane; bp 130-140 
(1.0 mm), mol wt 224 (ms), nmr, 0.73 (3H, s, methyl) 0.9-1.8 (23H, m 
CH.sub.2 CH, methyl .alpha. to hydroxyl), 1.75 (1H, s, hydroxyl), 3.51 (m, 
H.alpha. to hydroxyl, cis-isomer), 3.91 (m, H.alpha. to hydroxyl, 
trans-isomer); ir, 3380, 2940, 2870, 1455, 1380, 1070, 940 cm.sup.-1. 
EXAMPLE II 
Preparation of pure cis-1-(.alpha.-Hydroxyethyl)-4-t-butylcyclohexane and 
pure trans-1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane. 
The followig example illustrates how the pure isomers can be prepared. 
A mixture of cis and trans 1-acetyl-4-t-butylcyclohexane as prepared in 
Example ICla was separated into its pure components by vacuum distillation 
on a Nester-Faust spinning band distillation apparatus. The physical 
constants of the two isomers are as follows: 
cis-1-Acetyl-4-t-butylcyclohexane: mol wt 182 (ms); bp 
84.degree.-86.degree. C. (8 mm); 0.80 (9H, s, t-butyl H), 2.12 (3H, s, 
acetyl methyl H); ir, 1710, 1365, 1355, 1175, 1140. 
trans-1-Acetyl-4-t-butylcyclohexane: mol wt 182 (ms); bp 
92.degree.-93.degree. C. (8 mm); nmr, 0.85 (9H, s, t-butyl H), 2.10 (3H, 
s, acetyl methyl H); ir, 1710, 1365, 1250, 1168. 
The cis isomer was epimerized in a refluxing solution of sodium carbonate 
in aqueous methanol to a 90%:10% mixture of 
trans:cis-1-acetyl-4-t-butylcyclohexane. The spectral data of this mixture 
was essentially identical with that obtained for the pure trans isomer. 
Each of the pure 1-acetyl-4-t-butylcyclohexane isomers were converted to 
their respective alcohols with lithium aluminum hydride as described in 
Example ICla. The physical constants of the two isomers are as follows: 
cis-1-(.alpha.-Hydroxyethyl)-4-t-butylcyclohexane: mol wt 184 (ms); bp 
75.degree.-77.degree. C. (2 mm); nmr, 0.85 (9H, s, t-butyl H), 1.0-1.8 (13 
H, m, methyl d at 1.22, J=6 Hz), 3.93 (1H, m, H.alpha. to OH); ir, 3330, 
1365, 1240, 1235, 1065, 935, 880. 
trans-1-(.alpha.-Hydroxyethyl)-4-t-butylcyclohexane: mol wt 184 (ms); bp 
80-85 (2 mm); nmr, 0.85 (9H, s, t-butyl H), 1.0-1.8 (13 H, m, with methyl 
d at 1.16, J=6.5 Hz), 3.53 (1H, m, H.alpha. to OH); ir, 3340, 1365, 1235, 
1150, 1068, 950, 940, 930, 900, 880. 
The desirable sandalwood odorant properties of 
1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane are due predominantly to the 
cis isomer. 
The foregoing result may create a presumption that the cis isomer of other 
analogs described herein would be preferred over the corresponding trans 
isomers. Such data was not obtained, however, since no commercially 
feasible way of separating the isomers was known and since the mixture has 
a fine odor in itself. 
EXAMPLE III 
Preparation of 1-(.alpha.-hydroxyalkyl)-4-t-alkylcyclohexanes from 
1-alkanoyl-4-t-alkylbenzenes. 
The procedure for preparing 1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane 
from 4-t-butylacetophenone is offered for illustration. Other 
1-(.alpha.-hydroxyalkyl)-4-t-alkylcyclohexanes can be similarly prepared 
from the appropriate 4-t-alkylacetophenones. 
(1) cis and trans-1-(.alpha.-Hydroxyethyl)-4-t-butylcyclohexane from 
4-t-Butylacetophenone 
A mixture of 17.6 g (0.10 mol) of 4-t-butyl-acetophenone, 1.3 g of 5% 
rhodium on alumina, a few drops of acetic acid, and 10 ml of absolute 
ethanol was hydrogenated on a Parr apparatus under a hydrogen pressure of 
50 psi at ambient temperature until hydrogen uptake ceased. By glc, the 
hydrogenate contained 8% of 1-acetyl-4-t-butylcyclohexane. The catalyst 
was then removed by filtration and the above procedure repeated until 
hydrogen uptake again ceased. The mixture was filtered, concentrated under 
reduced pressure, and distilled to give 16.8 g (91% yield) of a 1:1 
mixture of cis- and trans-1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane. 
The spectral properties were the same as described in Example I. 
The same result was obtained when the solvent was acetic acid, ethanol, or 
pentane, or when the catalyst was 5% rhodium on charcoal, or when the 
temperature was 60.degree., or when the pressure was 300 psi. 
The same result was obtained when 1-(.alpha.-hydroxyethyl-4-t-butylbenzene 
was hydrogenated instead of 4-t-butylacetophenone. 
Rather than repeat the hydrogenation to remove the small amount of 
1-acetyl-4-t-butylcyclohexane present in the initial hydrogenate, this 
impurity can be removed from the 
1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane by vacuum distillation. 
EXAMPLE IV 
This example provides a general procedure for preparing the compounds of 
this invention according to path D of Chart I. 
The procedure for preparing 1-(.alpha.-hydroxypropyl)-4-t-butylcyclohexane 
is offered for illustration. The other analogs can be similarly prepared. 
(1) 1-(1-Hydroxypropyl)-4-t-butylcyclohexane 
To a mixture of 24 g (1.0 mol) magnesium turnings and 100 ml anhydrous 
ethyl ether was added 109 g (1.0 mol) bromoethane. The resulting solution 
was heated under reflux for two hours. To the above solution, 109 g (0.9 
mol) 1-formyl-4-t-butylcyclohexane was added dropwise over 1 hour. After 
addition, the mixture was heated under reflux for four hours, allowed to 
cool, and then added to 100 ml of a mixture of saturated ammonium chloride 
solution and ice. The mixture was extracted with ether (3.times.100 ml) 
and the extract washed with water, dried, concentrated, and distilled to 
give a 1:1 mixture of cis and 
trans-1-(1-hydroxypropyl)-4-t-butylcyclohexane: 116 g (66% yield); bp 
89-95 (1 mm); mol wt 198 (ms); nmr 0.85 (12 H, s, methyl H), 3.1-3.9 (1H, 
broad, .alpha.H); ir, 3350, 1364, 970. 
(2) 1-(.alpha.-Hydroxy-2-methylprop-1-yl)-4-t-butylcyclohexane 
This compound was similarly prepared using 2-bromopropane. Distillation of 
the product yielded a 1:1 mixture of cis and 
trans-1-(1-hydroxy-2-methylprop-1-yl)-4-t-butylcyclohexane; 77 g, 73% 
yield; bp 98-110 (3 mm); mol wt 212 (ms); nmr, 0.82 (15 H,s, t-butyl and 
isopropyl methyl H), 3.0-3.8 (1H, broad, .alpha.H); ir, 3360, 1360, 1110, 
1000, 980. 
EXAMPLE V 
This example, along with the following examples, is offered to illustrate 
the utility of this invention in fragrance compositions. 
The compounds of this invention are particularly useful in the creation of 
synthetic sandalwood oil substitutes or sandalwood specialties. In the 
following formulation, X represents a compound of this invention or the 
odorless diethyl phthalate. The diethyl phthalate is used to illustrate 
the formulation without the novel compound. 
______________________________________ 
X 200 
*Sandela.RTM., 50% in Diethyl phthalate 
700 
Amyris Oil 50 
American Cedarwood Oil 50 
1,000 
______________________________________ 
*Registered Trademark of Givaudan Corporation for a polycyclic alcohol 
product having a sandalwood odor. 
X can represent any of the novel compounds of this invention, each of which 
makes a contribution to the composition. By comparing the compositions 
containing one of the novel compounds with the composition wherein X is 
the odorless diethyl phthalate, the contribution is quite evident. 
While each of the novel compounds offer subtle differences of degree in 
their contribution, the odor of the composition without the novel compound 
is weaker and less reminiscent of the natural sandalwood oil. 
As expected from their individual odor strengths, the contribution of the 
compounds where R.sub.1 is methyl is stronger than those where R.sub.1 is 
a higher analog. 
Especially preferred in this formulation were those compounds having the 
more intense odors, i.e., 1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane, 
1-(.alpha.-hydroxyethyl)-4-(2-methylpent-2-yl)cyclohexane, 
1-(.alpha.-hydroxyethyl)-4-(3-methylpent-3-yl)cyclohexane, or 
1-(.alpha.-hydroxyethyl)-4-(1-methylcyclopentyl)cyclohexane. 
With other analogs, e.g., 
1-(.alpha.-hydroxyethyl)-4-(1-methylcyclohexyl)cyclohexane, 
1-(.alpha.-hydroxyethyl)-4-(3-ethylpent-3-yl)cyclohexane etc., it may be 
preferred to use higher levels in the formulation, perhaps 30 to 40%. 
The above formulation and discussions with respect to it are provided 
purely for illustration. It is expected that in each case the compound (or 
mixtures of them) chosen as X would be subject to the individual perfumers 
perferences and needs. The experienced perfumer would be expected to use 
his expertise to take advantage of the subtle nuances by which each of the 
compounds differ in compounding a new formulation. 
Depending on the perfumer's needs, compounds of this invention can be used 
in a range of concentration from 10-60% by weight. 
EXAMPLE VI 
The following example is offered to illustrate the utility of the 
sandalwood compositions of this invention in fragrance compositions of the 
woody type. Once again, in the formulation below, X is used to represent a 
novel compound of this invention or an equivalent amount of the odorless 
diethyl phthalate. 
______________________________________ 
Component Pts 
______________________________________ 
X 280 
Oranger liquid 20 
Limonene 38 
Linalool 66 
Linalyl acetate 95 
Benzyl acetate 20 
.gamma.-Methyl ionone 152 
p-tert.-Butylcyclohexyl acetate 
114 
Vetiver acetate 115 
Coumarin 40 
Versalide.RTM.* 30 
Aldehyde C-12, 10% DPG 4 
Undecalactone, 10% DPG 6 
Diphenyl oxide 10 
Diphenyl methane 10 
Total 1,000 
______________________________________ 
*Registered Trademark of Givaudan Corporation for 
1,1,4,4tetramethyl-6-ethyl-7-acetyl-1,2,3,4-tetrahydronapthalene. 
Compositions containing 1-(.alpha.-hydroxyethyl)-4-t-butylcyclohexane, 
1-(.alpha.-hydroxyethyl)-4-t-amylcyclohexane, and 
1-(.alpha.-hydroxyethyl)-4-(3-methylpent-3-yl)cyclohexane were compared 
with the formula wherein X was diethyl phthalate. In each case, the novel 
compound of this invention made the odor richer and smoother, and had an 
effect similar to that achieved by adding natural sandalwood oil. 
Other compounds of this invention can be used with similar results. Higher 
concentrations can be used in such a formulation for unique and special 
effects. 
EXAMPLE VII 
The following example is offered to illustrate the utility of the 
sandalwood compounds of this invention in fragrance compositions of the 
woody-floral type. As before, X represents either the compound added or 
the odorless diethyl phthalate. 
______________________________________ 
Component Pts 
______________________________________ 
X 300 
Amyl cinnamic aldehyde 21 
Aldehyde C-12 (Lauric) in 10% 
Dipropylene glycol 8 
Benzyl propionate 25 
Bergamot natural 22 
Methyl phenyl carbinyl acetate 
14 
Linalool, coeur 35 
Ylang bourbon extra 14 
.gamma.-Methyl ionone 100 
Jasmin synthetic 35 
.alpha.-Methyl-.beta.-(p-tert-butylphenyl)propion- 
aldehyde 70 
p-tert-Butylcyclohexyl acetate 
97 
Vetiver acetate 97 
3,7-Dimethyl-7-octenol 56 
1,1,4,4-Tetramethyl-6-ethyl-7-acetyl-1, 
2,3,4-tetrahydronaphthalene 
56 
Undecalactone, 10% in Dipropylene 
glycol 8 
______________________________________ 
The formulation with X as 
1-(.alpha.-hydroxyethyl)-4-(1-methylcyclopent-1-yl)-cyclohexane was 
compared with the one that had X as diethyl phthalate. The odor of the 
fragrance having the novel compound was richer and smoother than the 
fragrance without it. The effect achieved by the addition of the novel 
compound was similar to the effect achieved by the addition of natural 
sandalwood oil. 
In a similar fashion, other compounds of this invention can be used as X 
with similar effects. 
EXAMPLE XIII 
The following example illustrates the utility of the novel compounds of 
this invention in fragrance compositions of the muguet type. The term X 
represents a novel compound of this invention or the odorless diethyl 
phthalate. 
______________________________________ 
Component Pts 
______________________________________ 
X 142 
Aldehyde C-9, n-nonanal, 10% diethyl 
phthalate 2.3 
Aldehyde C-10, n-decanal, 10% DEP 
1 
Amyl cinnamic aldehyde 13 
Benzyl acetate 25 
Benzyl salicylate 20 
Cinnamyl acetate 45 
Cyclamen aldehyde, .alpha.-methyl-p-isopro- 
pylphenylpropionaldehyde 10 
Citronellyl acetate 30 
Phenyl methyl carbinyl acetate, 10% DEP 
45 
Hexyl cinnamic aldehyde 20 
Indole, 2,3-benzylpyrrole, 10% DEP 
4 
Laurine.RTM. , Hydroxycitronellal 
120 
Linalool, coeur 140 
Linalyl cinnamate 40 
Nerol, prime 40 
Phenyl ethyl alcohol 130 
Phenyl ethyl isobutyrate 4 
Phenyl ethyl dimethyl carbinol 
10 
Phenyl ethyl phenyl acetate 
25 
Rhodinol, extra 60 
Rhodinyl acetate 34 
Terpineol 50 
Tetrahydrolinalool 30 
1,000 
______________________________________ 
The addition of 
1-(.alpha.-hydroxyethyl)-4-(1-methylcyclopent-1-yl)cyclohexane as X above 
imparts a naturalness to the composition by imparting woody and stem notes 
thus making the odor more of the whole flower in its natural environment. 
The effect is reminiscent of the contribution made by natural sandalwood 
oil. The composition with diethyl phthalate as X lacks such qualities. 
Other novel compounds of this invention can be used as X with similar 
effects.