Stereospecific Synthesis and Conformational Analysis
of the 2-(p-Tolylsulfonyl)-4-t-Butylcyclohexanols
A DISSERTATION PRESENTED TO THE GRADUATE COUNCIL OF
THE UNIVERSITY OF FLORIDA
IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE
DEGREE OF DOCTOR OF PHILOSOPHY
UNIVERSITY OF FLORIDA
The cyclohexane structures and the nomenclature used in this
dissertation are those customarily used by the journals of the
American Chemical Society. Likewise, the manner of listing tech-
nical works in the bibliography is the customary one used by the
journals of the American Chemical Society. The abbreviations of
journals are those adopted by Chemical Abstracts.
All temperatures are reported in degrees Centrigrade, and
the Centigrade symbol is omitted. All melting points are reported
The author wishes to express his appreciation to many people for
their contributions to this research problem. He gratefully acknowl-
edges the advice and assistance of Dr. William H. Jones, chairman of
the Supervisory Committee and director of this research. Special
thanks is given to Commander Nathan L. Smith for the use of his time,
his chemicals, his equipment, and his knowledge of chemistry over the
past few years. For their valuable suggestions, the author would also
like to acknowledge his fellow graduate students and members of the
faculty of the Chemistry Department.
This research was carried out in part under a grant from Re-
search Corporation, whose support the author now acknowledges.
Finally, the author would like to acknowledge his wife for her
patience and her encouragement over the years this research was being
done, for drawing the structures used in the dissertation, and for
many other favors too numerous to list.
TABLE OF COiiTE1CIT
PREFACE . . . . . . . .
LIST OF FIGURES . . . . . . . . .
I. I1TRODUCTIO: . . . . . . .
II, RESULTS AID DISCUSSION . . . . . . .
A. 2 *(p-Tolylsulfonyl)*4 ct-butylcyclohexanol . 6
B. 2c*(p-Tolylsulfonyl)-4c-tabutylcyclohexanol . 15
C. 2t*(p-Toly1sulfonyl)-4t-t-buty1cyclohexano1 . 18
D. 2 -(p-Tolylsulfonyl)-4 *t-butylcyclohexano1 . 21
Eo cis* and trans-2*(p-Toly1sulfonyl)*4*t-butyl-
cyclohexanone 4 .4 . . . . a 0 a 23
FP The Ester Derivatives of the 2-(p-Tolylsul-
fonyl)-4-t-butylcyclohexanols . . . 28
G. Elimination Reactions . . . . . . 32
III EXPERIMENTAL . . 4 . . . . . . 35
IV, SM-i2MRY . I . . . . . . . 62
V6 BIBLIOGRAPHY . . . . . . 65
LIST OF FIGURES
3.. . . 6 6 6 .0 0 .. .. .... .. 9
4., 0. 6 0 0 0 0 0 *. 0 S 6 5 6 0 0 0 0 14
6. 0.. w 6 6 .. . . . . 174
6.. * * *. . . . . . . 4, 20
7 o * ** 0 0 0 21
. * . . 2
8 . . . . . . . .6 25
9* * * 0' . 0 . .. 25
10 . . . . . . . . 32
11. 0 s i . .. . . . ., 33
The conformations of a molecule according to Barton are "those
arrangements in space of the atoms of the molecule which are not
superposable upon each other" (1). Our concern with conformations
arose because of an interest in the study of elimination reactions
which may proceed through a carbanion intermediate--the ElcB elimi-
nation reaction mechanism (2,3). Of particular interest were the
stereoelectronic requirements necessary for such a mechanism, but
these requirements could not be examined without first finding a
proper system to study. The design and construction of a system con-
taining the necessary prerequisites for a study of the stereoelectronic
requirements of the ElcB elimination thus became a problem of some
Such a system would have to be a conformationally fixed or con-
formationally rigid system, and it must contain a functional group
which can readily participate in an elimination reaction. Also, a
carbon atom adjacent to the carbon atom holding this functional group
must have substituted on it a strong electron-withdrawing group capa-
ble of activating the hydrogen atom also present on this carbon. An
additional consideration is that the system imist be one which will en-
able some subsequent investigator to carry out kinetic determinations
of the elimination reactions.
Most of the work done in the field of ElcD elimination reac-
tions prior to this study has been concerned with the cyclohexane
and cyclopentane derivatives (4-10). A conformationally fixed cyclic
system would, therefore, provide an excellent starting point. An
answer to this was presented by Uinstein and Holness (11) who had
shown that the t-butyl group acts as a compelling group to keep the
cyclohexane ring locked in one conformation. Other large substituent
groups perform a similar function, but, for reasons to be submitted
later, the t-butylcyclohexane derivatives were selected as a conven-
ient starting point. Ilith this selection, an additional prerequisite
had to be introduced--ths t-butylgroup must be removed as far as
possible from the reaction site.
l!any functional groups have been utilized in the study of
elimination reactions. In order to select a functional group for this
system, a projection into the future of the problem became necessary.
Winstein and Holness succeeded in establishing the conformations of
the cis- and trans-4-t-butylcyclohenanols and the cis- and trans-3-
t-butylcyclohexanols (11). There appeared to be a possibility of
using these established conformations as an aid to determine the con-
formations of this projected system. This in turn dictated that the
functional group should be an ester. It was decided that the tosylate
group fit the criteria for ease of elimination and adaptability to
Choosing the remainder of the system presented no difficulty
as Bordwall and his co-morkers (4) have shown that the aryl sulfonyl
group is a strong electron-trithdrawing group capable of increasing
greatly the acidity of a hydrogen attached to the same carbon atom.
Availability of a reasonably pure intermediate was the dominant fac-
tor in selecting the p-tolylsulfonyl group as the group to use.
It then became necessary to put these components together to
see if the resulting system or systems satisfied all the criteria
prescribed and also to see if the preparation of such a system was
feasible. In review, we had decided that the basic structure should
be 3-t-butylcyclohexanol or 4-t-butylcyclohexanol with a p-tolylsul-
fonyl group substituted on a carbon atom adjacent to the carbon con-
taining the hydroxyl group and as far removed from the t-butyl group
as possible. Two structures fit this description:
OH SO2 CH3
S SO2 -CH3 OH
Fig. 1 I II
2-(p-Tolylsulfonyl)-4-t-butyl- 2-(p-Tolylsulfonyl) -5-t-butyl-
The final system, of course, would be the tosylate ester derivative
of the selected alcohol.
As mentioned before, a t-butyl group will keep the cyclohexane
ring locked in one conformation--the chair conformation--with the
large substituent in the equatorial position. This means that there
will be four possible geometric arrangements of the remaining two
groups: (A) hydroxsyla adal sulfone axial (B) hydroxyl aial
sulfone equatorial (C) hydroxyl equatorial, sulfone a:dial
(D) hydroxyl equatorial, sulfone equatorial. Re-ardless of which
system (I or II) was selected, the problem was to isolate and to
establish the conformations of each of the four geometric isomers.
Of course, it was recognized that each of the geometric isom rs, in
addition, could be represented by a pair of optical isomarso but we
were not concerned with resolving the optical isomers in this piece
Preliminary investigations indicated that the 4-t-butylcyclo-
hexanol system may be the more convenient system with which to work.
On the basis of this preliminary work it was decided that the prepa-
ration of the stereoisomeric racemates, the dl-2-(p-tolylsulfonyl)-
4-t-butylcyclohexanols should be undertaken. The four proposed iso-
mers can be represented by the following structures:
t-Bu t Bu SO-Ar
I-A S 0Ar "2
t-Bu t-Bu SO -Ar
cA -Ar 2
In order to name these compounds, a system of nomenclature was
borrowed from Curtin and Harder (12). Under this system I-A is 2 *
(p-tolylsulfonyl)-4c-t-butylcyclohexanol, 1-B is 2c*(p-tolylsulfonyl)-
4 -t-butylcycloheuanol, I-C is 2c-(p-tolylsulfonyl)-4 tt-butylcyclo-
hexanol, and I-D is 2 *(p-tolylsulfonyl)*4 tt-butylcyclohexanol.
Throughout the remainder of this work the names of the isomrs trill
be abbreviated according to a system also introduced by Curtin and
Harder. .First the position of the sulfone group relative to the hy-
droxyl group is indicated, followed by the position of the t-butyl
group also relative to the hydroxyl group. Thus, 2 -(p-tolylsulfonyl)-
4c-*tbutylcyclohe:anol is abbreviated "trans, cis-I."
Of the four suggested isomers, those of greatest interest for
subsequent elimination studies are trans cis-i (Fig. 2-IA) and
trans. trans-I (Fig. 2eID), since only these two compounds meet the
requirement of hnvin- the acidic hydrogen and the hydroxyl is,.
Cis cis-I (Fig. 2-IB) should undergo elimination rapidly to give the
trans-elimination product by a concerted or E2 elimination mechanism.
Ci trans-I (Fig. 2-IC) may also prove to be of interest because,
even though the groups involved in the elimination reaction are trans
to each other, the departing anion group is in the unfavorable e.ua-
torial conformation (1).
II. RESULTS AID DISCUSSION
A. 2 -(p-Tolylsulfonyl)-4c-t-butylcyclohesanol
Borduell and Kern (4) have reported the preparation of tran .
2-(p-tolylsulfonyl)-cyclohexanol by the oxidation of trans.-2-(p-
toluenethio)-cyclohexanol. The latter compound was prepared by the
reaction of eyclohoe:ene oxide with the sodium salt of p-toluenethiol,
From this sequence of reactions it app sred that 4-t-butylcyclohexane
oxide might be a useful intermediate in the preparation of transj
ci*s-I. Cyclohexene o:xides can be made from the corresponding cyclo-
hexene derivatives, so the preparation of 4-t-butylcyclohexene seemed
to be a convenient starting point for the synthesis of tr c3is-I.
Winstein and Holness (11), in their 7ori: on the t-butyl-cyclo-
hoxane derivatives reported the preparation of 4-t-butylcyclohexene
from 4-t-butylcyclohexanol by the Chugaev reaction, and this method
was adopted for our work. Starting with a commercial mixture of cis.
and trans-4-t-butylcyclohexanol, the ::anthate esters were prepared and
then decomposed to give a 40% yield of 4-t-butylcyclohexeno. 3eeauoe
of the rather obvious disadvantages of preparing olefins in large
amounts by the CTrigaev route and because of the comparatively lot
yields, an alternate route for the formation of our olefin was sought.
The most noteworthy of the attempts was the dehydration of the alco-
hols with phosphoric acid. An excellent yield of olefin was obtained,
but a comparison of the infra-red spectra of the products from the two
reactions indicated that the phosphoric acid dehydration product con-
tained materials not present in the Chugaev reaction product. Analy-
sis by gas chromatography showed one peak for the Chugaev reaction
material and two peaks for the phosphoric ac.d dehydration material.
The second product might well have resulted from a carbonium ion
rearrangement to a five-membered ring (13). However, no attempt was
made to characterize this material. As a result of this side reaction,
this and similar types of dehydration reactions were discarded as pos-
sible methods for the preparation of 4-t-butylcyclohexeno.
The second step in the synthesis of trans. cis-I involved the
formation of 4-t-butylcyciohexene oxide from 4-t-butylcyclohexene.
This was first accomplished by the reaction of the cyclohexene with
perbenzoic acid. However, this method required too much time for the
small amount of oxide obtained, and peracetic acid was used in place
of perbenzoic acid. Peracetic acid gave higher yields of epoxide
than were obtainable with perbenzoic acid and permitted the handling
of larger amounts of material. In addition, peracetic acid was a
commercially available product.
A liquid, b.p. 76-770 at a reduced pressure of 8 1/2 mmn. with
an odor reminiscent of menthol was the product formed from the reac-
tion of 4-t-butylcyclohexane with either perbenzoic acid or peracetic
acid. The product from the perbenzoie acid reaction showed two peaks
of comparable size when analyzed by gas chromatography. This indi-
cated that the ciSe and tIans isomers were formed in almost equal
amounts. These isomers could not be separated by distillation, and
no further attempts at separation were made.
The next step in the synthesis of the first isomer was the break-
ing open of the epo:dde ring by the sodium salt of p-toluenethiol.
Reactions of nucleophilic reagents of this type with epoxides are
know to proceed with trans opening of the epoxide ring* Since the
starting cpe::ide was a mixture of cis and trans isomers and since each
isomer has two reaction sites, then four possible products can be
postulated from the 1al opening (Fig. 3).
However, Barton (1) gives the generalization that the opening
of eposides should afford the diaxial product. In this case then, the
opening should occur in such a way that the hydroxyl and sulfide sub-
stituents in the product are in the aerial position (with the t-butyl
group remaining equatorial.) According to this scheme, the trans-
epoxide should open to give 2 t(p-toluenethio)-5 tt-butylcyclohexa-
nol (transg trans-VI) and the cis-epoxide should open to give 2t-
(p-toluenethio)-4c-t-butyleyclohexanol (a, is.y-V). The cis-
epoxide should thus produce the product that is desired (Fig. 3).
The product obtained from the reaction of the mixture of cis.
and trans-4-t-butylcyclohexene oxide with the sodium salt of p-
toluenethiol was a viscous oil which was purified by distillation,
b.p. 161-163 at a reduced pressure of appronimatoly 0.4 mm. A num-
ber of attempts were made to separate the isomers by distillation,
crystallization, and formation of ester derivatives, but none of these
attempts were successful. It therefore became apparent that the
Fig. 3 Trans Opening of Epoxides
isomers would have to be separated after the sulfides had been o*i-
dized to the corresponding sulfones.
The oil which was presumably a mixture of the isomeric sulfide
alcohols was oxidized by hydrogen peroxide in glacial acetic acid.
The resulting product was dissolved in an ethyl acctata-hc anc mix-
ture. Fron this solution, a hitch c crystalline solid was collected in
35% yield. The solid was recrystallized to a melting point of
121-122 The presence of a sulfone group was established from its
infra-red spectrum by a very strong absorption at 8.7-8.8 microns and
by another strong absorption at 7.6-7.8 microns (14). The latter ab-
sorption actually consists of three peaks but it was not determined
whether all three peaks or only one or two of the peaks could be at-
tributed to the sulfone group. Elemental analysis substantiated the
conclusion that this compound was one of the isomeric sulfone alco-
In order to establish the structure and geometrical configura-
tion of this material, it was decided that the coa.ound should be de-
sulfurized. The fragment of the molecule remaining after desulfuri-
zation had occurred should be either 3-t-butylcyclohezanol or 4-t-
butyleyclohexanol. Further, unless the hydroxyl group was epimerized
during the reaction and assuming Barton's rule holds, the fragment
should be either grtas-3-t-butyleyclohexanol or cis-4-t-butylcyclo-
heranol. The conformations of these alcohols had already been estab-
lished by tinstein and Holness (11). Therefore, it was recognized
that if the desulfurized product could be related to one of the
!linstein and Holness' conformers, then the conformation of the sul-
fono alcohol under question could be unequivocally established. De-
sulfurization was accomplished by the use of Raney nickel tith 75%
ethanol as the solvent. The product isolated from this reaction had
a melting point of C'-32o 0 indicating that it was 4-t-butyleyclohexa-
nol and not 3-t-butylcyclohenanol. A mixture of this material with
pure trans-4-t-butylcyclohexanol gave a malting point of approxi-
mately 65-72o. Analysis by gas chromatography showed a good pea! for
cis-4-t-butylcyclohesanol with a very small peak for the trans-alcohol.
This is understandable since the trans-alcohol is more stable and
some equilibration is possible during the course of the reaction.
The conclusion to be reached from this evidence is that since cis-
4-t-butylcyclohexanol was obtained from the desulfurization reaction,
then the starting material must be gan, cs-I and not tran,
Additional desulfurizations were later carried out with similar
results. Several other solvents were also tried, and in some of
thbse, such as benzene and toluene, the desulfurization reaction was
not successful. But with one solvent, very interesting results were
observed. When the reaction was carried out in dio::ano, the product
was identified as a mixture of cis- and trans-4-t-butylcyclohexanol
(the cis-alcohol present in greater amount) along with some 4-t-butyl-
cyclohexanone. The id:el-catalyzed conversions of alcohols to alde-
hydes and ketones has been reported, but most of these conversions
were carried out at higher temperatures (15, 16). The reaction was
not studiMcE any further, but its unusual behavior set a precedent
for the observation of several unusual reactions which subsequently
occurred with the sulfone alcohol system.
Anticipating that a large amount of ray, cjgs-I would be needed,
the oxidation of the sulfide mixture was repeated under a variety of
conditions in an attempt to increase the yield of the desired product.
An examination of the residue from the original oxidation indicated
that along with the isomeric sulfone alcohols there were also ketones
present. In addition, during the work-up of the reaction, a certain
amount of decomposition appeared to be taking place whenever the
material was heated. To eliminate the formation of the ketones and
the decomposition of product, an oxidation reaction was carried out
at 0 0 Within a short time a solid was formed. The infrared
spectrum of this solid did not show the characteristic sulfoac ab-
sorption nor did it compare favorably with the spectrum of the start-
ing material. On recrystallization, the solid separated into two
fractions. The largest fraction melted over a very wide range, but
the first fraction collected was a reasonably pure material with a
melting point considerably higher than that of the tagen cis-I com-
pound. This fraction was recrystallized to a melting point of
173-1740. The infra-red spectrum of this compound showed a strong
absorption peak at 9.6 microns which corresponds to the absorption for
sulfoxide compounds (14). Elemental analysis also indicated that the
compound was a sulfoxide. It then became necessary to establish the
structure of this sulfoxide. This was accopliabhel by furt=ie- oxida-
tion of the sulfozide to the sulfone. The only product isolated from
this reaction was ttr.s cis-I although, as suspected, there was ke-
tone preoont in the residue. Based on this evidence, the starting
sulfoxtide was determined to be 2 -(p-toylsulfinyl)-*4 .t-butylcyclo-
hexanol (str cnin-7II). A later o-:idntion of this culfo:nide gave
a 92% yield of crude tr.n., cis-I with very, little contamination from
Attempts to isolate the isomeric sulfotide by fra=tional crys-
tallization were not successful, as was indicated by the fact that
the products always melted over a wide r=inc. However, it must be
concluded that the material with the wide malting renge was a mixture
of the isomeric sulfo::ides rs, ci-*III and ranrs trans-IV.
Further o::idation of this material gave a quantitative yield of crude
product from which a 40% yield of trans cisaI vas obtained.
When the information from the various reactions was assembled,
some insight into the problems concerned with the oxidation of the
sulfides to the sulfones was gained. Since a variety of materials
were present in the product, it became very easy to draw conclusions
about the difficulty in obtaining the desired crystalline product.
In, another att2nnt to prepare trgans cia-I, the reaction of 4-
t-butylcyclohexene o :ide with sodium p-toluenesulfinate was examined.
From this reaction only one product, m.p. 164-1650, was isolated. The
infra-red spectrum of this compound showed the characteristic sulfone
absorption and the elemental analysis of the comiound showed that it
1) No H
3) Me I
R- 0-OHu _
tB -Bu -V
t-Bu t-Bu CIS-vi,
TRANS, CIS- V
TRANS, C IS-1
TR ANS,TRANS- II
Fig. 4 Sequence of Reactions for Preparation of trans, cis-I and trans, trans-II
was an isomeric p-tolysulfonyl-t-butyleyclohexanol. This compound
should be trangy trans-II, but further work will have to be done in
order to assign it this conformation. The formation of this single
product can be explained by an examination of molecular models which
indicate that the reaction site in the trans*epoxide might well be
less hindered than the reaction site in the cis-epoxideo The sul-
finate group is a rather bulky group, so the storic factors would be
::pected to play a greater part in this reaction than in the opening
of the epoxide with the sulfide. This reaction shows come promise as
a starting.point for work on the 2-(p-tolylsulfonyl)*5-t-butylcyclo-
B. 2 -(p-Tolylsulfonyl)-4 -t-butylcyclohexanol
In tans# cis-I, the sulfone group is in the axial position,
which from steric considerations is a less favored position than is
the equatorial position. Therefore, if the proton on the same carbon
is removed to form a carbanion, then the sulfone group should equili-"
brate to the less hindered equatorial position. Since the sulfone is
a strong electron-irithdrawing group, the ccrbanion should be formed
rather easily in a base of sodium ethoxide. In the first attempt to
carry out this opimerization reaction, trans. cis-I was added to so-
dium ctho;:ide and the resulting solution refluxed for an hour.
This type of reaction is well known, so no difficulties were an-
ticipated. The product from this first reaction was a solid, m.p.
100-1010. The infra-red spectrum of this compound contained the
characteristic sulfone absorptions but did not contain the absorption
associated with the hydro:;1l group. Instead, the spectrum had an ab-
sorption at approximately 6.09 microns, indicating that an olofin had
been formed. This was confirmed by elemental analysis.
A second epimerization was then atte.-tcd at 25o. The product
from this second reaction was a white solid, m.p. 134-1350. The infra-
red spectrum of this compound showed both the sulfone and hydroxyl ab-
sorptions but was quite different from the starting material. Thus,
apimcrization had apparently occurred. This was also confirmed by
Since the hydroxyl group would be expected to retain its geo-
metric configuration during the epimerization reaction, the cis
cSie- structure was tentatively assigned to this new alcohol. An
attempt to confirm this conclusion by Raney nickel desulfurization
was unsuccessful. When the Raney nickel desulfurization of the
epimer was carried out in dioxane, a mixture of cis- and trans-4-t-
butylcyclohexanol resulted. That the hydro:yl group actually did
remain in the wjial position was confirr_-c later both by comparison
with the trans trans-I isomer (this being the other isomer with the
sulfone group in the equatorial position) and by chemical evidence to
be presented in another section.
The dehydration that occurred during the first attempt at epimeri-
zation came as a surprise because ordinarily the hydro.yl group cannot
be removed under basic conditions. However, this observed dehydration
closely parallels the dehydration that occurs in certain aldol type
Fig. 5 Epimerization of trans, cis-I
compounds. Hauser and Breslo:7 (17) studied the mechanism of elimina-
tion of water from organic compounds in the presence of base using an
aldol. They proposed a stepwise meachnism involving first the re-
moval of a P-proton, followed by the loss of the hydroxyl group from
the resutling carbanion and the oimultaenous shift of electrons to
form the olefin. One of their conclusions was that water appears to
be eliminated from organic compounds in the presence of strong bases
only wihan the hydrogen on the P-carbon atom is highly activated by an
electron-withdrawing group. This requirement is certainly achieved.
Furthermore, their suggested mechanism might well be operating in the
case of the dehydration of the sulfone alec ..
C. 2t (p-Tolylsulfonyl) 4t-t-butylcyclohexano1
In view of the fact that cis-2-(p-tolylsulfonyl)-4-t-butyl-
cyclohexanone (cis-IX) could be rather readily obtained,1 the route
which wea picked to puruse for the synthesis of the tri-equatorial
isomer, trans, tan-I, was the stereoselective reduction of this
ketone. Diborane was selected as the reducing agent for two reasons.
First, Jones (18) has recently reported that the diborane reduction of
4-t-butylcyclohexanona gives almost exclusively the equatorial alcohol
(over 90%7), and second, Brown and Subba Rao (19) have reported that
the sulfone group is not affected by diborane. It was thus felt that
by using diborane to reduce cis-IX, we should obtain predominantly a
lThis will be discussed in more detail later.
product with the hydrb~:y group in the equatorial position, Th.n re-
duction was carried out by bubbling diborane into a solution of cis-IX
in tetrahydrofuran until the carbonyl absorption of the ketone dis-
appeared. The borate ester was hydrolyzed in water to produce an al-
cohol, mip. 115-1160. Again, elemental analysis substantiated the
conclusion that this material was one of the isomeric sulfone alco-
From a consideration of the fact that the ketone which produced
this isomer had the sulfone group in the euatorial configuration,
and the fact that this material was quite different in its properties
from cis cs-I, there can be little doubt but that this new isomer
has the structure pictured in trans trans-I. Furthermore, the infra-
red spectra of the two isomers assigned structures cis, is- and
trans. trrns-I were decidedly different, neither spectrum containing
all of the absorption peaks present in the other. This ruled out the
possibility that one of the materials could be an eutectic mixture of
cis.is-I and trans trans-I. In addition, there was ample evidence
supporting the use of diborane as a stereoselective reducing agent.
Despite the compelling nature of the evidence on hand for the
assigned structures, there did remain open two questions which w% felt
deserved further consideration. Could the hydroyl group have been
introduced into the axial position during the diborane reduction of
cia-LL? And, could the hydroxyl group have been epimerized in the
sodium ethoxide solution at the same time the sulfone group was
epimerized? Results reported by other investigators, some of which
have already been cited, suggest that both of these questions should
be answered in the negative. That this is a correct presumption v as
demonstrated as follows (Fig. 6): If the a:ial hydroyl group had
epimerized with sodium ethoxide, then the product front the reaction
of Lrans, .cis- with sodium ethoxide should have been the isomer with
all three groups in equatorial positions (Fig. 6 A). If this were the
case, then the isomer produced by the reduction of ci L-IX must have
the hydroxyl group in the axial position (Fig. 6 B). The possibility
that these two things had occurred was eliminated by subjecting the
latter isomer to the same conditions under which the former isomer
had been prepared.
Thus, if sodium othoxide had equilibrated both the sulfone and
the alcohol groups in trans cs-I, then it would certainly be ex-
pected to have the same effect on the isomer resulting from the re-
duction of the ketone. This, of course, would result in formation of
the same product that was obtained when trans cis,-I was treated with
N Et OH
A. t- t-Bu SO-Ar
B. B2 H6
t-Bu SO2-Ar t-Bu SO-Ar
In actual fact, treatment of the alcohol in question with sodium
ethoxide yielded only unreacted starting material, alons 7ith a small
amount of olefin which was detected in the infra-red spectrum of the
crude reaction product. As a result of this e:perimcnt, we could say
that the hydroxyl group was not cpimerized in sodium ethoxido, and
that the cpimarisation of trans. cis-I had produced the gS Sis--I
isomer (Fig. 5). The second conclusion that could be dranm from this
experiment was that the diborano reduction had introduced the hydroxyl
group into the equatorial position, and the isomer resulting from this
reduction has the structure pictured for trans, trans-I (Fig. 7).
rO ^1) -2 H 6 I/ 4 OH
t-Bu SOAr 2) H20 t-8 -Ar
Fig. 7 cis-IX transg, transI
The Ss tans I isomer has proved to be the most difficult to
prepare, and up to this time its synthesis and isolation have not been
accomplished. Many attempts were made to prepare this isomer by
several different paths, but none proved successful. However, some
of these routes, even though unsuccessful, are of sufficient interest
to warrant discussion. Apparent in these methods are some reasons for
the difficulties encountered in .past attempts, and it is hoped they
may. provide some ideas for future attempts to isolate the s trans-I
Since the trans, traLs-I isomer had been prepared by the reduc-
tion of cis-2-(p-tolylsulfonyl)*4*t-butylcyclohexanone (cgi-IX), it
was felt that the cig, trans-I isomer could be prepared by the reduc-
tion of the trans-ketone (transI-x0 ) Unfortunately, only a very small
quantity of the trans-IX isomer was available. The reduction of this
ketone was attempted under conditions similar to those for the reduc-
tion of the cis*IX isomer, but the small amount of product collected
could not be identified. A mixture of ci*- and jrans-IX was then re-
duced with diborane. It was hoped that both isomeric ketones would
be reduced and that a separation of the alcohol isomers could then
be effected. Two products were isolated from this reaction. One was
trans Jras-"I, which was expected, and the other was pure trgasyIX
which was not expected. This meant, at best, that the reduction of
trans-IX was a considerably slower reaction than the reduction of
An entirely different path for the preparation of is tang-I
was then examined. This path involved the reaction of 2 tbromo-4t *t
butylcyclohexanol (trans, -an-XI) with sodium p-toluenesulfinate.
The trans, trans-XI compound had been prepared by the reduction of qi-
2-bromo-4-t-butylcyclohexanone (cis-X). Substitution of the bromo
group by the sulfinate group under S,2 conditions would be expected to
give the desired cips trans-I compound. Several reactions were tried
under a variety of conditions, but none of these were successful. The
lack of success of this particular reaction can be explained by the
steric hindrance encountered by the approaching sulfinate group.
A third path examined as a possibility for the preparation of
iS trans-I started with the tosylate ester of trans cis-I, It was
hoped that acetolysis of the ts cis.-I tosylate night produce the
acetate ester of cis, trans-I. Ester interchange reactions are knovm
to proceed with inversion of configuration. For example,.trans-4-t-
butylcyclohoxyl acetate has been prepared by the acetolysis of cis.4-
butylcyclohesyl p-toluenesulfonate. Hydrolysis of the cis etrIns-I
acetate should then produce the fourth sulfone alcohol. However,
even under severe conditions, no acetolysis was observed with the
tosylate. Again, a variety of conditions were used, but no acetate
was ever isolated.
The latter two of the above-mentioned paths must be considered
closed as possible routes for the synthesis of cis. trans-I. The
one that still looks promising is the reduction of the ketone trans-
IX. The important step still needed here is to find a suitable
method for the preparation of the ketone intermediate* Once this prob-
lem has been worked out, it should be possible to prepare the missing
E. cis.- and transa-2(p-Tolylsulfonyl)-4-t-butylcyclohexanone
The outline which was drawn up listing the possible routes by
which the isomeric 2-(p-tolysulfonyl)-4-t-butylcyclohexanols could be
synthesise showed that thn isomers of 2-(p-tolylsulfonyl)-4-t-butyl-
cyclohexanone might be useful intermediates in the synthesis of at
least two of the racemates. Thus, the preparation, isolation, and
characterization of cis- and tr-an-2- (p-tolylsulfonyl)-4-t-butylcyclo-
hexanone had to play a prominent role in this investigation.
It was felt that the csi cis-I isoner could be o::idlTed to the
cis-ketone and that this ketone could then be reduced to the t-an-
trans-I raceriate. This series of reactions was observed, although a
vore convenient source of the cis-ketone was found. Likewise, it was
felt that the trans cL-! racemate could be oxidized to the transom
ketone and that this could then be reduced to the ie atrnsIo
racemate. The reduction of the trans-hetone has not yet been ob-
aerved, but, as pointed out before, this appears to bo the aost feas-
ible route for. o'tainin^ the cis trans-I isomer. The greatest dif-
ficulty to date has been the anomalies encountered in the o::ldation
of the trans cis-_I compound.
The oxidation of the trans cis-i compound was first carried out
us.ng chronic anhydride in glacial acetic acid. The product from this
reaction was a white solid, m.p. 143-1440. Originally thil compound
was thought to be the trans-ketone. But, the same ketone was obtained
when the epimer, c, ci-I, was oxidized under similar conditions.
This product was tentatively assigned the structure depicted for the
csi-ketono. One explanation offered for the formation of the same
product from both of the epimers was that under the acidic conditions
used for the oxidation, the ketone was forimd and then converted to
the enol, Since the onol is planar, the ketone which was regenerated
from the anol was the one in which the sulfone group was in the more
stable equatorial position.(Fig, 8).
Fig* 8 cis- Eis-I
That this was indeed the cis-ketone was later verified when the
same product was prepared by the reaction of trans-2*bromo-*4t-butyl-
cyclohexanone (transo* ith sodium p.,toluenesulfinato under Sy2 condi-
tions. An SN2 reaction would) of ciirso, produce the ketone cis-IX.
+ No S2O"- CH3 -.
t-Bu O -Ar
Fig. 9 trans-X
Since the same product was obtained from these three different reac-
tions, there was no question but that the ketone under question was
The reaction of sodium p-toluenesulfinate with trans-2-bromo-
4-t-butylcyclohexanone had been a rapid reaction and had given a good
yield of product. Prom this information it appeared as if sodium p-
toluonesulfinate ought to react with cis-2-bromo-4-t-butyleyclo'e:::-
none to give the ketono trans-IX. IIowever, when this rciction was
carried out under the same conditions as the previous reaction, no
sulfone ias formed, and the bromoketone, cis-NX, was recovered, Uhan
the reaction time was increased considerably, a low yield of the
ketone cis-IX was obtained. This was not too surprising in view of
the steric factors involved in attempting a backside displacement of
the equatorial bromine.
The best method for preparing the ketone trans-IX appeared to
be the oxidation of trans, c-I under the proper conditions. Thus,
an extensive search was conducted to try to find the necessary condi-
tions. A great number of conditions were tried, but the first success
was encountered with the use of activated gZarencs dioxide in a nou-
tral solvent. In one reaction with manganesa dioxide, a ne:w ketone,
m.p. 127.5-128.50, was obtained. Since the analysis and the infra-red
spectrum of this compound confirmed the assumption that it was a sul-
fone ketone, it had to be the tgans-ketone. Unfortunately, when the
reaction was repeated on a larger scale, no oxidation was observeS.
Since then the reaction has been attempted many times with no success.
Apparently, slight changes in the conditions are enough to keep the
oxidation from going, and we have not been successful in repeating
the precise set of conditions which seem to be necessary.
All of the oxidations which were carried out in acid media gave
the epimerised ketone. Strong basic conditions could not be used be-
cause ie already had evidence that the sulfone group epimerized under
strong basic conditions. But, there was still the possibility that in
a weak basic media the sulfone group would retain its configuration.
So, an oxidation reaction was carried out using chronic anhydride in
pyridine. Even under these mild conditions, however, the c.is-hetone
was produced. Perhaps this should have been expected because the
effect of the carbonyl group would be to make the P-hydrogen atom more
acidic than in the sulfone alcohol, thus permitting the weaker base to
extract the proton and allowing the sulfone group to again epimerize.
DurinS the course of our search for the proper act of conditions
needed to oxidize tganso 2gl-I to the tran-ketone, we had varied the
oxidizing agent, the media in which the reaction was conducted, and
the temperature at which the reaction was conducted. In an attempt
to determine if our assumption that the trans-hetone was formed and
was then equilibrated to the enol in an acidic media was correct, it
was decided that the time factor for the oxidation should be varied.
When the oxidation was carried out using sodium dichromate in dilute
sulfuric acid over a short time interval, a mixture of the cis- and
trans-ketones was produced. This gave some indication that our as-
sumption might be correct. The attempted reduction of this mixture
with diborane has been discussed in a previous section* The partial
success encountered in this case suggests that further investigation
of these condition as a route for the preparation of the trans-
ketone is warranted.
The Irans-ketone is desired because it is the intermediate which
we think will lead to the missing ci, trans-I isomer. In order to
prove this assumption, we must have enough of the trns-lhatone to a k:c
a study of its reduction rlith diborane feasible. The key, then, is
to find suitable conditions for preparing the trens-ketone in reason-
able amounts. We can only hope that this will be achieved in the near
F. The Ester Derivatives of the 2-(p-Tolylsulfonyl)-
With the exception of sterically hindered alcohols, the ester
derivatives of secondary alcohols can usually be prepared with little
difficulty in good yields. For e::ample, in the preparation of the
tosylate and phthalate esters of cis- and trans-4-t-butylcyclohe:-anol
(11), and in the preparation of the tosylate esters of ci-. and trans-
2*(p-tolylsulfonyl)-cyclohexanol (4), no problems were encountered.
On this basis one would anticipate that the esters of the sulfone al-
cohols should be easy to make. This was not the case. If the esteri-
fication reactions had gone as anticipated, there would be little value
to be gained from a discussion of the esters, and their preparation
would merely be reported in the experimental section. However, because
of the anomalies encountered, a discussion seems warranted.
The tosylates of the 4-t*butylcyclohexanols had been prepared
by mi::ing the appropriate alcohol with p-tolueneoulfonyl chloride in
pyridine at 00 for 24 hours. In the first attempt to make the tran--
cis-I tosylate, similar conditions were used except that the tempera-
ture of the reaction mixture was raised to 250. After 24 hours, the
tosylate Was collected in 62% yield. Eordcuall and Kern (4), in pre-
paring the tosylate of tran.-2-(p-tolylsulfonyl)-cyclohexanol had let
the reaction run for 7 days and had isolated an 82% yield of pure
tosylate. So, in an attempt to increase the yield, we permitted our
reaction to run for the same length of time. Ilouover, a slightly
lower yield resulted from the longer reaction time. This indicated
that perhaps some decomposition of the grans cis-I tosylate may have
occurred, but the difference in per ccnt yield was too small to per-
mit much speculation. Uhat is important here is to recognize that a
fair yield of the tras cis-I tosylate could be obtained with the
shorter reaction time.
There was the possibility that the sulfone group could have
epimerized during the esterification reaction. That this did not occur
was shown by dissolving trans cis-I in pyridine and allowing this mix-
ture to rcc in at 250 for 12 days. Only starting material was re-
covered from the solution, shioing that isomerization does not occur
in pyridine. Thus, pyridine apparently is not a strong enough base to
extract the P-proton from the sulfone alcohol.
The formation of the trans trans-I tosylate was attempted under
the same conditions, but no tosylate was formed when the reaction was
run for only 24 hour. After 5 days, some esterification had occurred,
but 50% of the starting material was recovered unchanged. I'ar lly,
one expects the equatorial alcohol to esterify at a faster rate than
the axial alcohol. The only explanation that can be given for the
difference seen in the reactivity between the trcan cis-I alcohol
and the trn'. m rans-I alcohol is that the acuatorial sulfone group
interferes to a greater extent with the incoming tosylate group than:
does the axial oulfone group.
Since the o::inl hydroxy opimer should esterify at a slower rate
than the equatorial hydrox:y epimer, it was predicted that the Ls
cis-I tosylate isomer should be more difficult to prepare than the
transg tr.nn_-I isomer. This was indeed the case. Up to this time the
tosylate of the Cji, cis-I alcohol has not been prepared. The esteri-
fication reaction has been run for lengths of time varying from 7 days
to 60 days, and as yet no trace of the tosylate has been detected.
Apparently, the steric compression of the axial hydroxyl group, due
to the 1:3 axial hydrogen interactions coupled with the 1:2 sulfone
interaction, is large enough to prevent the formation of the tosylate
under these conditions.
Again, there is an alternative to be considered for the failure
to detect any of the cis. cis*I tosylate. The alternative is that the
hydrolysis of this particular tosylate is extremely rapid and therefore
it is destroyed in the workup of the reaction product. This possibility
was eliminated by examining the infra-red spactrtm= of the reaction mix-
ture at various time intervals. No evidence was found to indicate that
the cis ciS.- to.*:late was ever fCorn2ed. Another indication that the
tosylate was not l.eiln formed was that no pyridinium chloride was ob-
served in the reaction :::iure2 Several attempts were made to pr'e.zre
the clsy -c I toaylate at higher temperaturuc, but none of those were
successful. Attempts to prepare the tosylate are still being made,
but it ia felt that another ester derivative will have to be used for
the elimination studies.
The acetate derivatives were fairly easy to prepare once it was
determined that higher temperatures and longer reaction times were
needed than are normally required. Likewrise, the mono-phthalate ester
of j rans cis-l had to be prepared using a higher terceraturn and a
longer reaction time than is normally required.
An attempt was made to prepare the acetate ester of is trans-I
by an ester interchange reaction with the trans cis-I tosylate.
That this reaction was not successful has already been mentioned.
The cis, tres-I acetate was desired as a possible intermediate for
the preparation of the cis trans-I alcohol. The alcohol could be pre-
pared by hydrolyzing the cSl, rans-I acetate. The trans cis-I
acetate was used as a working model to determine the conditions nec-
essary for an hydrolysis reaction. Lithium aluminum hydride was se-
lected as the hydrolyzing agent in order to prevent isomerization of
the alcohol during the hydrolysis reaction. Ilowever, instead of just
hydrolyzin3 the ester, the lithium aluminum hydride reduced the acetate
to the hydrocarbon (Fig. 10).
LiU Al H4 -SO-Ar
SO-Ar t- Bu
Fig. 10 jtrans cis-I acetate
No further work was done with this reaction, nor with other hydroly-
sis reactions, as the is. trans-I acetate was not available.
G. Elimination Reactions
As pointed out earlier, the system we have designed, prepared,
and characterized is to subsequently be used to study the kinetics of
the elimination reactions. Before the kinetics can be studied, how-
ever, it is necessary to determine whether or not elimination will
occur with all of the isomers and what product or products will be
formed by the elimination reaction. It was decided that a good sys-
tem for the elimination reactions might be to use dioxane as the sol-
vent and sodium hydroxide as the base. So, to check the products
formed by the elimination reactions, the tosylate esters were heated
with strong base in dionane.
An olefin had previously been obtained when the trans cis-I
alcohol was heated with sodium ethoxide. This same olefin was formed
when the cis, s-I* alcohol was placed in sodium ethoxide at room
temperature for a few days. Since the elimination from the cia, cis-I
alcohol was a trans elimination, and since the reaction most likely
proca'cad by an E2 mechanism, the olefin was assigned the structure
depicted for l-(p-tolysulfonyl)-5-t-butylcyclohe:xne (VIII).
t-Bu a Et
02- Ar AE
OH OEt vii
The trans cis-I .tosylate, when heated at 80 with 5 N sodium
hydroxide in dioxane, gave a quantitative crude yield of the same ole-
fin (VIII), which was recrystallized to give a 61% yield of the pure
product. Io material other than the blefin was detected in the crude
product. There are two possible mechanisms, EIcB and E2, by which the
elimination reaction could have proceeded. :oSever, explanations and
speculations concerning the mechanism of the elimination will be left
to the investigators who study the kinetics of the elimination reac-
The trans trans-I tosylate, when subjected to similar condi-
tions--heating with 5 II sodium hydroxide-- also underwent elimination,
alLiho'; a small amount of alcohol was formed, indicating that come
hydrolysis of the tocylate occurred before elimination took place.
In addition, there appeared to be two unsaturated products forrid
by the elimination reaction. On recrystallization of the crude
product, two olofin fractions were collected. These two products
had slightly different melting points and different infra-red
spectra, but, conflicting with this evidence, was the evidence that
no depression was observed in the mixed melting point and that the
nuclear magnetic resonance spectra of the two fractions wore vir-
tually identical. Again, this must be examined further when the
kinetics are studied. Of greatest importance to us is the fact that
elimination did occur when the tosylate group was in the equatorial
This section includes the experimental procedures for the posi-
tive results discussed in the previous section, as well as the nega-
tive results associated with the attempts to prepare 2c-(p-tolylsul-
fonyl)-4t-butylcyclohexanol and 2c-(p-tolylsulfonyl)-4cet-butylcyclo-
hoxyl p-toluenesulfonateo-the tosylate ester of cis. ci-I. The
latter experiments are included to enable other workers to see what
procedures have been tried and what procedures show promise for fur-
For many of the compounds, several reactions involving differ-
ent sets of conditions proved to be successful, but only one proce-
dure is listed. In all cases we have presented the procedure which
we feel is best for preparing that particular compound. A few of
the oxidation reactions of 2t (p-tolylsulfonyl)-4c-t-butylcyclohexa-
nol are given to help future workers in this area to avoid some of
the pitfalls we encountered.
Two procedures are listed for the preparation of 4-t-butyl-
cyclohexene oxide. This was done because the compound was first pre-
pared with the use of perbenzoic acid and it was this material which
was sent for elemental analysis. The epoxidation reaction was later
found to be more satisfactory with peracetic acid.
Elemental analyses were performed by Weiler and Strauss, 164
Banbury Road, Oxford, England, and by Galbraith Microanalytical Labora-
tories, P. 0. Box 4187, Knoxville 21, Tennessee.
Melting points have been reported uncorrected.
To a solution of 224 g. of 4-t-butylcyclohexanol in 1 liter of
anhydrous ether was added 47.6 g. of sodium hydride, and the mixture
was stirred for 24 hours. To the sodium alcoholato was added 152 ml.
of carbon disulfide over about an hour, and the resulting thick slurry
was stirred for an additional hour. Methyl iodide, 470 g., was added
and this mixture stirred for 18 hours, after which 50 ml more of
methyl iodide was added and stirring continued for 1 hour. The reac-
tion mixture was then filtered and the residue washed with ether.
The ether was removed by heating on a steam bath, leaving 314 g. of
a red oil which solidified on standing.
The oil was refluxed at 200-2100 for 2 hours, and the residue
from the decomposition of the xanthate was distilled, producing 117 g.
of light yellow oil at 69-730 (18 ma.). The oil was redistilled, and
81.7 g. (417) of product was collected at 73-75 (22 nm.). Reported
b.p. 65-66 (20 im.).
cis- and trans-4-t-Butylcyclohexene oxidel (cis. and trans-VII)
Method A. To 18.75 g. of 4-t-butylcyclohexane was added 300 ml.
1Since the completion of this work, the preparation of the mix-
ture of cia- and trans-4-t-butyl-eyclohexene oxide has been reported
by J. Sicker, F. Sipos, and 4. Tichy, Collection Czechoslov. Chem.Commun.,
26x 847 (1961).
of a chloroform solution containing approximately 22 g. of perbcnaoic
acid. The solution, which was shaken frequently during the first few
minutes, was then stored in a refrigerator for 24 hours, at which time
there was still an excess of peroxide present. The reaction mixture
ums shaken with 5% sodium hydroxide, washed with water, and dried
over sodium sulfate. The chloroform was removed and the residue dis-
tilled, producing a colorless, pleasant-smelling oil. The product
was redistilled through a Vigreaux column, yielding 14,0 g. (67%) of
product, b.p. 114ll16 (18 m.a).
Analysis. Calculated for C H10 0: C, 77*86; H, 11.76
Found: C, 77.59; H, 11.83
Method B. A solution of 40.0 g. of 4-t-butylcyclohexene in
200 ml. of chloroform was cooled in an ice bath. To the stirred
solution was added, dropwise over a 30-minute period, 90 ml4 of per-
acetic acid containing 8 g. of sodium acetate trihydrate. After addi-
tion was completed, the ice bath was removed and the solution stirred
for one more hour.
The reaction mixture was poured into ice water and the aqueous
layer extracted with chloroform. The combined chloroform layers were
washed with 10% sodium carbonate, then with water, and then were dried
over sodium sulfate. The solvent was removed and the residue distilled.
This product was redistilled, yielding 36.5 g. (82%) of the epoxide,
b.p. 76-77o (8 1/2 Emm.).
Reaction of the mixture of epoxides (cis- and trans-VII) with p-tolu-
enethiol. 2t.(p*Toluonethio)-4c-t-butylcyclohexanol (trans, cis V)
and 2t*(p-toluenethio)-St-butylcyclohexanol (trans trans-VI)
To 49.7 g. of p-toluenethiol in 200 ml. of 50% ethanol was added
16.0 g. of sodium hydroxide, and the mixture was stirred until all of
the sodium hydroxide had gone into solution. To the stirred solution
was slowly added 59.9 g. of 4-t-butylcycloheoene oxide, stirring being
continued for 3 hours. The reaction mixture was poured into water and
then extracted with chloroform. The organic extracts were uashed with
water and then dried over sodium sulfate, The solvent was removed,
leaving 107.5 g. of crude product. This impure product was distilled,
yielding 95.7 g. (88%) of product, b.p. 161-163 (approximately
2 *(p-Tolyloulfonyl)-4 ct-butylcyclohexanol (trans cs-I)
To 1.31 g. of the mixture of sulfides (trans, ci-V and transg
trans-VI) dissolved in 20 ml. of glacial acetic acid was added 20 ml.
of 30% hydrogen peroxide, and the mixture was heated for 6 hours at
80-90 The reaction mixture was cooled, poured into water, and ex-
tracted with chloroform. The chloroform extracts werewashed with
10% sodium bicarbonate and with water, and then dried over sodium sul-
fate. The solvent was removed, leaving a light brown oil as the resi-
due. The oil was dissolved in ethyl acetate, cooled, and hexane added
to the solution until it turned cloudy. The solution was then cooled
to 0, producing 0.79 g. of a solid contaminated with oil. The solid
was recrystallized from an ethyl acetate-hexane mixture, yielding
0.52 g. (35%) of fairly pure material, m.p. 117-1200. Further re-
crystallizations produced a material, m.p. 121-1220.
Analysis. Calculated for C17112603S C, 65.77; H, 8.44; S, 10.33
Found: C, 65.71; H, 8.42; S, 10.16
2 -(p-Tolylsulfinyl)-4 ct-butylcyclohexanol (trans. cis-III).
A solution of 95.7 g. of the mixture of sulfides (trans. cis-V
and trans trans.VI) dissolved in 150 ml. of glacial acetic acid was
cooled in an ice bath. To the stirred mixture was added 120 ml. of
30% hydrogen peroxide over a 30-minute period. Stirring was continued
for 6 hours after addition was completed. During this time a white
solid separated from the solution. The reaction mixture was filtered,
yielding 15.5 g. of material, m.p. 95-1170. Water was added to the
filtrate, the mixture stirred for a short time, and again filtered
to remove the solid that had formed. This time 103.3 g. of material
contaminated with acetic acid was collected. The filtrate from the
second solid was extracted with chloroform and the chloroform extracts
worked up in the usual way. When the solvent was removed, 14.3 g. of
oil, which later solidified, was collected. The infra-red spectra of
the three solids appeared to be similar, but there were noticeable
differenceslin relative peak heights. However, the characteristic
sulfone absorption peaks were not present in the spectrum of any of
Recrystallization of the solids from ethyl acetate-hexane
mixtures produced a series of solids, each with a different =cltint
point range. The fractions collected from the recrystallisation of
the second solid were typical: Fraction I, 9.2 g., m.p. 163-167;
Fraction II, 5.9 g., m.p. 150-161; Fraction III, 32.7 g., m.p. 74-135;
Fraction IV, 4.0 g., m.p. 85-112. The infra-red spectra of there :
solids indicated that the sulfoxide had been formed. Further re-
crystallizations of Fraction I yielded a material, m.p. 173-174.
Analysis. Calculated for C172602S: C, 69.34; U, 8,90; S, 10.$3
Found: C, 69.32; II, 9.03; S, 11.03
Further oxidation of this material with hydrogen peroxide gave
a 90% yield of trans cis-I thus proving that the sulfoxide which
was isolated was 2 .(p-tolylsulfinyl)-4 -t-butylcyclohexanol. When
the oxidation was carried out by heating on the steam bath for
several hours, the yields of trans cis-I decreased and a ketone was
detected in the residue.
Attempts tWere made to isolate 2 t-(p-tolylsulfinyl)-5 -t-butyl-
cyclohexanol from Fractions III and IV, but none of these attc,-ts
were successful. Further oxidation of these fractions gave low yields
of trans c-I.
Reaction of the mixture of epoxides cEs- and trans-VII with sodium p-
toluenesulfinate (20), 2t-(p-Tolylsulfonyl)s5t-t-butylcycloho:anaol
To a solution of 21.4 g. of sodium p-toluanesulfinate in 50 ml.
of 50% aqueous ethanol was added a solution of 14.8 g. of the cia.
trans epo::ide mixture (cis- and trans-VII) in 50 ml. of 50% aqueous
ethanol. The reaction mixture was stirred for 24 hours at room tem-
perature, then more water was added and the mixture heated gently for
4 hours. The reaction mixture was poured into water, extracted with
ether, and the ether extracts worked up in the usual manner. The
solvent was removed, leaving 21.3 g. of product which was a mixture
of a solid and an oil. This mixture was filtered and the solid re-
crystallized from an acetone-water mixture, yielding a material,
m.p. 143-1570, ,whose infra-red spectrum showed the characteristic
sulfone absorptions. Further racrystallizations from ethanol yielded
a material, m.p. 164-165 0
Analysis. Calculated for C17 2603S: C, 65.77; 0, 8.44; S, 10.33
Found: C, 65.73; H, 8.28; S, 10.38
Epimerisation of trans cis-I. 2c-(p-Tolylsulfonyl)-4 -t-butylcyclo-
hexanol (cia, cis-I)
1.0 g. of trans cis-I was added to 25 ml. of absolute ethanol
which contained 400 mg, of sodium, and the reaction mixture was allowed
to remain at room temperature for 2 days. The reaction mixture was
poured into cold dilute hydrochloric acid and extracted with chloro-
form. The chloroform extracts were washed with water and then dried
over sodium sulfate. The solvent was removed, leaving a yellow oil.
Tha oil wa5 dissolved in ethyl acetate and heated with a little Norit
to remove the yellow color, From this solution was collected 0,50 g.
of solid, m.p. 130-133. Mixed m.p. with trans cias-I, 107-110. The
infra-red spectrum differed from that for trans cis*I. Further re-
crystallizations from ethyl acetate yielded a material, m.p. 134-1350.
Analysis. Calculated for C17260 3: C, 65.77; HIj 8.44; S, 10.33
Found: C, 65.68; II, 8.60; S, 10.43
Reaction of transg cis-l with sodium etho:ide at an elevated tc-era-
ture. 1- (Tolylsulfonyl) -5-t-butylcvyclohoeeno (VIII)
To 25 ml. of absolute ethanol which contained 400 mg. of sodium
was added 1.0 g. of trans cis-I. The solution was refluxed for 1
hour, and then allowed to cool for an hour before being poured into
ice water to which a small amount of hydrochloric acid had been addcd.
The aqueous mixture was extracted with chlcroform. The chloroform
extracts were washed with water and then dried over sodium sulfate.
The solvent was removed, leaving an oil. The oil was diszolvcd in
hoxane and cooled, producing a solid, m.p. 95-96.50, The infra-red
spectrum of this material did not have the absorption peaks for an
alcohol, but instead, showed an absorption for a carbon-carbon double
bond. Further recrystallization from hexane yielded a material,
Analyl7s* Calculated for C17 ,,,0,S: C, 69.82; 11, 8.27; S, 10.96
C, 69.62; II, 8.06; S, 11.11
Oxidation of rains, eis-I with chromic anhydride (11). cis.2-(p-Tolyl-
sulfonyl*4 t-butylcyc lohexanone (cis-LX)
To a solution of 1.0 g* of trans. cis-I in 10 ml* of glacial
acetic acid was added a solution of 1.0 g. of chronic anhydride in
25 ml. of glacial acetic acid. The reaction mixture was allowed to
remain at room temperature for 34 hours. The mixture was poured into
water and extracted with chloroform. The chloroform extracts were
washed with 10% sodium bicarbonate, then with water, and dried over
sodium sulfate. The solvent was removed, leaving a residue which was
a mixture of an oil and a solid. The infra-red spectrum of the resi-
due showed a carbonyl absorption. The residue was shaken with ether
to remove the oil, leaving 0.2 g. of solid, m.p. 133-139 Recrys-
tallization from ethyl acetate yielded a material, m.p. 143-1440.
Analysis. Calculated for C1711243S: C, 66.20; 11, 7.84; S, 10.39
Found: C, 66.38; H, 7.84; S, 10.36
Oxidation of tran cis.I with activated manganese dioxide (21). trans-
2-(p-Tolylsulfonyl) -4-t-butylcyclohexanon: (rga-OIX)
To 5.2 g. of activated manganese dioxide was added a solution of
3.1 g. of tran cis-I dissolved in 50 ml. of dry benzene. -The mix-
ture was stirred for 19 hours. The infra-red spectrum showed a car-
bonyl absorption and a very small hydroxyl absorption. The mixture
vas allowed to remain for an additional 12 hours, after which it was
filtered and the menganose dioxide washed with benzene. The solvent
was removed and the residue taken up in aqueous ethanol. From this
solution wtas collected a total of 1.1 g. of product, m.p. 120-124.
Further recrystallizations from ethanol yielded a material, m.p. 127.5-
Analysis. Calculated for C17 2493S: C, 66.20; HI, 7.84; S, 10.39
Found: C, 66.23; HI, 7.80; S, 10.41
Oxidation of trans$ cis-I with sodium dichromate. Mixture of cis- and
trans-2-(p-tolylsulfonyl)-4-t-butylcyclohexanone (cis- and trans-IX)
To a solution of 4.77 g. of sodium dichromate dihydrate dissolved
in 30 ml. of water was slowly added 3 ml. of concentrated sulfuric
acid and the resutling mixture cooled to 400. To this solution was
added 5.0 g. of trans cir-I in approximately 1.0 g. portions. Reac-
tion was indicated by a change in color of the solution and the for-
mation of an oil on the top of the solution. The temperature of
the reaction mixture was kept at 80-90 during the addition of the
alcohol. The mixture was allowed to cool for 30 minutes at room tem-
perature after the last portion had been added. The reaction mix-
ture was poured into water and extracted with chloroform. The organic
layers ware worked up similar to those in the chromic anhydride oxi-
dation. The oil remaining after the solvent had been removed was
dissolved in ethanol. From this solution was collected 3.1 g. of
solid Ahich melted over a xide range. This solid was recrystallized
from ethyl acetate, giving a product, m.p. 93-105. The infra-red
spectrum of this product showed a ccrbonyl with a doublet. The
spectrum indicated that the product was a mixture of cis- and trans-
IX. Further recrystallization produced 3 fractions: Fraction A,
m.p. 115-131; Fraction B, m.p. 107-1250; Fraction C, m.p. 104-115.
The infra-red spectra of these fractions showed that reaction A had
a greater concentration of cig-IX than the mi:nture, and Fractions B
and C had a lower concentration of cis-IX than the mixture.
An attempted diborane reduction of Fractions B and C produced
reasonably pure trans*-X plus a second fraction that included ketone
and alcohol which wore not separated.
Oxidation of transg cls-I with chronic anhydride in pyridine (22). cis-
2.(p-Tolylsulfonyl) -4*t-butylcyclohex.anol (cigXsI)
To 50 ml. of pyridine at 100 was added 5.0 g. of chromic anty-
dride. To the chronic anhydride-pyridine co-mplex was added, at room
temperature, a solution of 5.0 g. of trans cis-I in 50 ml. of pyridine.
The mixture was allowed to remain at room temperature for 24 hours.
The reaction mixture was filtered to remove the brown preiciptate that
had formed, poured into water, and then extracted with other. The
ether extracts ware washed with dilute hydrochloric acid, then with
water, and dried over sodium sulfate. The solvent was removed and the
resulting oil crystallized from ethanol, giving a good yield of the
Oxidation of 2c*(p-tolylsulfonyl)-4c-t-butylcyclohcxanol (cis. cis-I).
A solution of 0.9 g. of cis, cis-I in 10 ml. of glacial acetic
acid was added to a solution of 1.0 g. of chromic anhydride in 30 ml.
of glacial acetic acid. The mixture was allowed to remain at room
temperature for 48 hours before being poured into water. The aqueous
mixture was extracted wiith chloroform, and the chloroform extracts
washed with 10% sodium bicarbonate, then water, and dried over sodium
sulfate. The solvent was removed, and the oil produced taken up in
ethyl acetate. From this solution was formed 0.3 g. of a solid,
m.p. 134-138. The infra-red spectrum of this solid was identical with
the spectrum of the ketone from the oxidation of trans cis-I with
chromic anhydride. Pecrystallisation of the solid from ethyl acetate
yielded a material, m.p. 141-1420. lxized melting point with cis-IX,
Mixture of cis- and trans-2-bromo-4-t-butylcyclohexanone (cis- and
The mixture of cis- and trans-2-bromo-4-t-butylcyclohexanone was
prepared by the method of Allinger and Allinger (23). To a cooled,
stirred mixture of 154 g. of 4-t-butylcyclohexanone in 300 ml. of water
was added dropwise 160 g. of bromine. The addition took about 75 min-
utes, and stirring was continued until the bromine color disappeared.
The reaction mixture was extracted with ether, and the ether extracts
washed with 10% sodium bicarbonate and water, then dried over sodium
sulfate. The solvent was removed--the solution cannot be heated to re-
move the ether since decomposition of trans-X occurs readily--produc-
ing a pale yellow liquid. The liquid was distilled as rapidly as pos-
sible, using the lowest pressure obtainable with the vacumn pump. Ex-
tra sodium hydroxide traps were needed as decomposition of the bromo-
ketones occurred throughout the entire distillation. The temperature
at which product was collected varied widely because.of fluctuations in
the pressure due to the decomposition& From this distillation 121 g.
of product which was contaminated with HBr was collected.
The mixture of bromoketones had to be either used immediately or
else worked up to remove the cigsX isomer because decomposition of the
trans-X isomer occur-c.1 even at 0. The cis-IX isomar uwa isolated by
dissolving the mixture of isomors in pentane and cooling. The cis-X
isomer, m.p. 68 could be stored in the refrigerator without decom-
Reaction of tr-ans-2-bromo-4-t-butylcyclohexanone (trans-X) with sodium
To a solution prepared by dissolving 21.0 g. of the oil remaining
from the mixture of eis- and trans-X, after the cis-X isomer had been
removed, in 50 ml. of ethanol was added 14.4 g. of sodium p-toluene-
sulfinate and the mixture stirred overnight. A heavy precipitate
formed in the reaction mixture. Water was added to the mixture and
the precipitate removed by filtration, giving 23.7 g. of crude product.
The product was recrystallized from ethyl acetate, yielding a mater-
ial, m.p. 142-1440, whose infra-red spectrum was similar to that for
Sis-IX. Mired melting point with cis-IX, 142-144.
Reaction of cis-2-bromo-4-t-butylcycloheranone (cis-X) with sodium p-
To a solution of 2.2 g. of sodium p-toluenesulfinate in 50 ml.
of ethanol was added 2.2 g. of cis-X. The mixture was stirred over-
night, and was then diluted with 100 ml. of water. The precipitate
which formed was filtered, giving 0.5 g. of a material, m.p. 125-135.
The infra-red spectrum of this material indicated that it was the cis-
IX sulfone ketone. Recrystallization from ethyl acetate yielded a
material, m.p. 141-1420. li:xed melting point with cis-It, 141-143.
The yield from this reaction was very poor compared to the yield
from the reaction of trans-X with codiun p-toluensulfinate under the
same conditions. In a second reaction, the yield was raised by greatly
increasing the time the reaction was allour-d to runi In this reaction,
10.2 g. of cis-X and 10.4 g. of sodium p-toluenesulfinate were dissolved
in 250 ml. of ethanol and stirred for 9 days. Water was then added and
the reaction mixture stirred overnight. The reaction mixture was fil-
tered, giving 11.0 g. of product, m.p. 141-143o Mixed melting point
with cils-X1 142-144o. Tih infra-red spectrum of the product was vir-
tually identical with that for cis-IX.
Reduction of cis-2-(p-tolylsulfonyl)-4-t-butylcyclohexanone with di-
borane. 2t-(p-Tolylsulfonyl)-4t-t-butylcyclohexanol (trans trans-I)
A solution was prepared by dissolving 1.5 g. of cis-IX in 25 ml.
of tetrahydrofuran. The solution was placed in a cooled reaction flask
equipped with a bubbler, a magnetic stirrer, and an outlet tube to an
acetone trap. The system was swept with nitrogen and then diborane
bubbled into the solution until no more carbonyl absorption was ob-
served in the infra-red spectrum. The diborane generator flask was
heated gently to remove all the diborane, and the system again was swept
with nitrogen. The reaction mixture was poured into water, forming an
oil which solidified after a few minutes. The solid was filtered, giv-
ing a product, m.p. 115-116. The infra-red spectrum of this material
differed from those for trans. cis-I and cis. cis-I.
Analysis. Calculated for C 1712603S: C, 65.77; H, 8.44; S, 10.33
Found: C, 65.96; II, 8.31; S, 10.32
Diborane was generated either by dripping boron trifluoride
etherate onto trimethylanine-borane (24) or be dripping a solution
of sodium borohydride in diglyme into boron trifluoride etherate (25).
Reaction of transj trans-I with sodium cthoxide
To 15 ml. of absolute ethanol containing 200 ma. of sodium was
added 0.5 s. of trans trans-I. This solution was allowed to remain
at room temperature for 28 hours. The reaction mixture was poured
into water and then workedd up in the same way as the product from the
epimarization of trans, cis-. The infra-red spectrum of the crude
product, m.p. 110-1130, showed that starting material was recovered
along with a very small amount of olefin. The crude product was re-
crystallised, yielding only trans, trans-I. The recrystallized prod-
uct was not weighed, but it appeared as if most of the starting ma-
terial had been recovered.
2 -(p-Tolylsulfonyl)-4 -t-butylcyclohexyl p-toluenesulfonate (trans
R tosyiate) ..... .. ...
To a solution of 5.0 g. of trans. cis-I in 20 ml. of dry pyri-
dine was added 3.8 g. of p-toluenesulfonyl chloride. The mixture was
allowed to remain at room temperature for 24 hours. The mixture was
poured into water and extracted with ether. The ether extracts were
succssively washed with dilute sulfuric acid, with sodium bicarbo-
nate, and with water. The solution was dried over sodium sulfate, and
the other removed under reduced pressure. The resulting oil was dis-
solved in a methanol-petroleum ether mixture and cooled, producing
4.6 g. (62%) of product, m.p. 114-122. Further recrystallinations
from ethanol yielded a material, m.p. 124-1250
Analysis. Calculated for C 243205S2: C, 62.04; IH, 6.9'; S, 13.80
Found: C, 61.99; H, 7.07; S, 13.86
Reaction of trans. cis-I with pyridine
A solution of 1.0 g,. of trans- cis-I in 10 l,. of dry pyridine
was allowed to remain at room temperature for 12 days. The reaction
mixture was worked up in the same way as the trnne, cis-I tosylate re-
action mixture. The infra-red spectrum of the crude material, m.p.
100-1440, showed that only the starting material was present. Re-
crystallization yielded a material, m.p. 119-1210. Mxed melting
point with trans, Ci-I, 119-1220. The trans cis-I isomer did not
isomerize in the pyridine solution.
2t-(p-Tolylsulfonyl)-4 -butylcyclohexyl p-toluenesulfonate (gans,
To a solution of 1.4 g. of trans trans-I in 15 ml. of dry pyri-
dine was added 1.1 g. of p-toluenesulfonyl chloride. The mixture was
allowed to remain at room temperature for 5 days. The reaction mix-
ture was then poured into a very dilute hydrochloric acid solution.
The solid that formed was filtered and washed with a 5% hydrochloric
acid solution. The solid was recrystallized from acetone, yielding
a material, m.p. 164-1650.
Analysis. Calculated for C2413205S2: C, 62.04; H, 6.94; S, 13.80
Found: C, 62.00; H, 6.91; S, 13.60
The filtrate from this reaction was extracted with ether and
the extracts worked up in the usual way, giving 0.7 g. of the start-
ing trans trans-I alcohol.
2t (p.Tolylsulfonyl)-4c-t-butylcyclohesyl acetate (trgan cis-I acetate)
To 30 ml. of acetic anhydride was added 2.0 g. of trans, cs-I
and the mixture heated on a steam bath for 5 hours. The reaction mix-
ture was poured into water and stirred. The solid which was formed was
filtered and dried, giving 1.9 g. (<.) of pnodntet, m.p. 104-1170.
Repeated recrystallizations from ethanol yielded a material, m.p.
Analysis. Calculated for C19112804S: C, 64.74; H, 8.01; S, 9.09
Found: C, 64.57; H, 7.82; S, 9.09
2 -(p-Tolylsulfonyl)-4 -t-butylcycloheryl acetate (cis, Jis_-I acetate)
Cis is-I, 0.4 g., was dissolved in 25 ml. of acetyl chloride
and reflu,;ed for 3 hours. The reaction mixture was poured into water.
An oil was formed which did not solidify even when cooled. The mix-
ture was extracted with ether and the ether extracts washed with 10%
sodium carbonate and water. The solution was dried over sodium sul-
fate and the ether removed, producing 0.5 g. of a yellow oil. The
oil was taken up in methanol. A yellow solid, m.p. 140-1450 was
crystallized from this solution when it was cooled in a refrigerator.
The solid was dissolved in ethanol and heated with Horit to decolor-
ise the solution. Further recrystallizations from ethanol yielded a
material, m.p. 145-*146.
Analysis. Calculated for C1912804S: C, 64.74; H, 8.01; S, 9.09
Found: C, 64.74; H, 7.84; S, 9.20
2 t(p-Tolylsulfonyl)-4 tt-butylcyclohexyl acetate (trans., trans-I
Tran trans-I, 0.5 g., was added to 20 ml. of acetyl chloride
and refluxed for 3 hours. The reaction mixture was poured into water.
The solid which formed was filtered and dried, giving 0.5 g. of prod-
uct, m.p. 136-1400. Recrystallization from ethanol yielded a material,
Analysis. Calculated for C19 2804S: C, 64.74; H, 8.01; S, 9.09
Found: C, 64.97; 1, 7.93; S, 9.03
When the a trans.rans-I alcohol was heated with acetic anhydride
for 6 hours on a steam bath, no reaction was observed.
2t-(p-Tolylsulfonyl)-4c-t-butylcyclohexyl hydrogen phthalate (trans,
To a solution of 5.0 g. of trans cis-I in 20 ml. of dry pyri-
dine was added 4.8 g. of phthalic anhydride, and the mixture was heated
on the steam bath for 9 hours. The reaction mixture was poured into
a dilute hydrochloric acid solution and cooled in an ice bath. After
a few hours, only an oil had formed, so the mixture was extracted with
ether. The ether extracts were shaken twice with sodium bicarbonate
for extended periods. The organic layer was discarded, and the aque-
ous layer acidified with dilute hydrochloric acid. The ester was re-
moved from the acid solution by again extracting with ether. The
ether extracts were washed with water and dried over sodium sulfate.
The solvent was removed, leaving a solid residue. The solid was re-
crystallized from ethanol, producing 5.3 g. (72%) of material, m.p.
165-174o. Repeated recrystallizations from ethanol yielded a mater-
ial, m.p. 177-178.
Analysis. Calculated for C25H3006S: C, 65.48; H, 6.59; S, 6.99
Found: C, 65.56; H, 6.54; S, 7.03
Desulfurisation of trans, cis- with Raney nickel (26,27)
Method A. A solution of 0.40 g. of trans. cis-I in 35 ml. of
75% ethanol was refluxed with approximately 8 g. of Raney nickel cata-
lyst for 7 hours. The mixture was filtered to remove the catalyst.
The solvent was removed, and the resulting oil taken up in hot hexane.
The hexane solution was filtered, concentrated to a small volume and
cooled. A small amount of solid was collected, m.p. 82-83. Mixed
melting point with trans-4-t-butylcyclohexanolp about 64-76. The
infra-red spectrum indicated that the product was cis-4-t-butylcyclo-
Pure cis*4-t-butylcyclohexanol and pure trans-4-t-butylcyclo-
hexanol were prepared from a commercial mixture by the methods of
Winstein and Ilolness(ll).
Method B* A solution of 0.5 g. of trans cis-I in 30 ml. of
75% ethanol was refluxed with approximately 9 g. of Raney nickel
catalyst for 9 hours. The mixture was filtered and the filtrate ex-
tracted with pentane. (A solid formed at the interface of the organic
and aqueous layers. The solid was filtered and identified as the
starting trans cis-I isomer. Approximately 0.2 g. of starting ma-
terial was recovered.) The pentane was removed, leaving a solid.
The solid was purified by sublimation, yielding a material, m.p.
80-82 A small amount of this material was dissolved in ether and
analyzed by gas chromatography. A nice peak was obtained for cis-t-
butylcyclohexanol, plus a very small peak for trans-t-butylcyclohexa-
nol. The infra-red spectrum of the material indicated that there was
slight contamination from the trans-alcohol.
The gas chromatographic analysis of this product, as well as
for the products of succeeding reactions, was made by using an 18
foot Tide detergent column (30-60 mesh, F and M Scientific Corpora-
tion), operating at 1600 and 30 pounds per squre inch of pressure.
Method C. A solution of 1.0 g. of trans cis-I in 100 ml. of
dry dioxane was refluxed with approximately 12 g. of Raney nickel for
19 hours. The mixture was filtered and the solvent removed. The solid
obtained was sublimed, producing a material, m.p. 48-64. Gas chromato-
graphic analysis of this material showed it to be a mixture of . s- and
trans-4-t-butylcyclohexanol (the cis-alcohol was present in the greatest
concentration) and 4-t-butylcyclohexanone. The infra-red spectrum
of this material confirmed the presence of the ketone.
Desulfurization of ci- cis-I with Raney nickel (26, 27)
A solution of 0.3 g. of cis. cis-I in 50 ml. of dry dioxane was
refluxed with approximately 8 g. of Raney nickel for 12 hours. The
mixture was filtered and the solvent removed. The resulting solid was
sublimed. The infra-red spectrum of the sublimed material indicated
that it was a mixture of cis- and trans-4-t-butylcyclohexanol con-
taminated with some 4-t-butylcyclohexanone.
Desulfurization of trans, trans-I with Raney nickel (26, 27)
A solution of 0.3 g. of trans trans-I in 50 ml. of dry dioxane
was reflu:ed with approximately 8 g. of Raney nickel for 13 hours.
The mixture was filtered and the solvent removed. The solid residue
was sublimed, producing a material, m.p. 56-610. Gas chromatographic
analysis of this material showed it to be a mixture of cis- and trans-
4-t-butylcyclohexanol (the trans-alcohol was present in slightly
greater concentration) plus a very small amount of 4-t-butylcyclolhexa-
Reaction of 2t.(p-tolylsulfonyl)*4c*t-butylccylohexyl p-toluenesulfon-
ate (trans, cis-I tosylate) with sodium hydroxide. Elimination reac-
To a solution of 0.358 g. of trans cis-I tosylate in 10 ml.
of dio:ane was added 1 ml. of 5 N sodium hydroxide, and the mixture
heated on a steam bath for I hour. The mixture was poured into water
and extracted with other. The ether extracts were washed with water
and dried over sodium sulfate. The solvent was removed, leaving a
white solid, m.p. 88-950 in almost quantitative yield. The infra-red
spectrum of this solid showed that the olefin has been formed. The
solid was recrystallized from hexane, yielding 0.148 g. (61%) of a
material, n.p. 99.5-100.5. The infra-red spectrum of this olefin
is the same as the spectrum for the olefin obtained when trans trans-I
was heated with sodium ethoxide.
Reaction of 2 -(p-toly1sulfonyl) 4-t-buty1cyclohe: y1 p-toluenesulfon-
ate (trans, trans-I tosylate) with sodium hydroxide. Elimination reac-
To a solution of 0.356 g. in 15 ml. of dioxane was added 1 ml.
of 5 1I sodium hydroxide and the mixture heated and stirred at 850 for
1 hour. The reaction mixture was poured into water and extracted with
ether. The organic extracts were washed with water and dried over so-
dium sulfate. The solvent was removed, leavin- an oil as the residue.
Pentate was added to the oil and a solid, m.p. 82-880, was formed. The
infra-red spectrum of this crude product showed that olefin had been
formed, but it also showed that a small amount of hydroxyl compound had
been formed. ;I'.-:,tallization of the solid from hexane yielded three
Fraction I, 120 ag., m.p. 103-1040. Mixed melting point with
the olefin from the elimination reaction of the trans cis-I tosylate,
99-103. The infra-red spectrum of this olefin differed from that for
the previous olefin in several peaks. The most noticeable differences
appeared in the 7.6-7.8 micron region, where there were differences in
the relative peak heights of three strong absorptions, and at 12.06
and 12.26 microns. One of the olefins showed a strong absorption at
12.06 microns, but no absorption at 12.26 microns, while the other
olefin showed a strong absorption at 12.26 microns, but no absorption
at 12.06 microns. However, the nuclear mrnintic resonance spectra
(courtesy of Dr* W. Brey, University of Florida) of the two products
showed no differences. A closer look will have to be taken at these
two products when more of the materials are available.
Fraction II, 14 m3., m.p. 88-95 The infra-red spectrum of
this product showed an hydroxyl absorption as well as an olefin simi-
lar to Fraction I.
Fraction III, 2.6 m.., m.p. 100-101o. The infra-red spectrum
of this fraction was similar to the spectrum for the olefin obtained
when trans, trans-I was heated with sodium ethoxide.
Reaction of 2 -(p-tolylsulfonyl)-4 -t-butylcyclohexyl acetate (trans,
cis-I acetate) with lithium aluminum hydride (28). 3-t-Butyl-(p-
To a stirred, cooled mixture of 0.41 g. of LiAlH4 in 25 ml. of
dry ether was added dropwise a solution of 0.69 g. of the trans cis-I
acetate in 25 ml. of dry ether. The mixture was stirred for 2 hours
after addition was completed. Very dilute hydrochloric acid solution
was added to decomrpoe the excess LiA1HI4, The mixture was extracted
with ether and the ether extracts washed with 10% sodium bicarbonate,
then with water, and then dried over sodium sulfate. The solvent was
removed, leaving a small amount of solid. Recrystallisation of this
solid from ethyl acetate yielded a material, m.p. 108-109. The infra-
red spectrum of this material showed no absorption for the hydroxyl
group and no absorption for the carbonyl group.
Analysis. Calculated for C17H2602S: C, 69.34; H, 8.90; S, 10.89
Found: C, 69.17; H, 8.74; S, 10.98
The elemental analysis and the infra-red spectrum showed that
LiA1H4 reduced the ester to the hydrocarbon. Io attempts ware made
to establish the stereochemistry of this particular isomer.
Reduction of cis-2-bromo-4-t-butylcyclohexanone (cis-X) with diborane
Diborane was bubbled into a cooled, stirred solution of 7.9 g. of
cis-X in 25 ml. of diglyme until the infra-red spectrum of the solution
showed the disappearance of the carbonyl absorption. The reaction mix-
turc was poured into water and extracted with ether. The ether extracts
were worked up in the usual manner. The solvent was removed, leaving
an oil as the residue. The infra-red spectrum of this oil showed a
strong hydroxyl absorption. A few attempts were made to isolate a
solid from this oil, all without success, so the impure material was
used for subsequent reactions. Although not isolated or characterized,
this material should be 2t -bromo-4 tbutylcyclohexanol (trans trans
Attempted reaction of 2 -bromo*4 -t-butylcyclohexanol (trans. trans-
XI) with sodium p-toluenesulfinate
Method A. Sodium p-toluenesulfinate, 2.4 g., was added to a
solution of 2.6 g. of the oil from the reduction of cis-2-bromo-4-t-
butylcyclohexanone in 25 ml. of diglyme, and the mixture heated on a
steam bath for 3 hours. The reaction mixture was poured into water and
extracted rith ether. The ether extracts were washed with water and
dried over sodium sulfate. The solvent was removed, producing 2.6 g.
of oil. The infra-red spectrum of this oil corresponded to that for
the starting material.
Method B. Sodium p-toluenesulfinate, 2.4 g., was added to a
solution of 2.6 g. of the oil which was suspected to be jtrans trans-
XI in 25 ml. of diglym, and the mixture was refluxed for 12 hours.
The reaction mixture was worked up in the same way as the reaction
mixture in Method A. Starting material was again recovered.
MIethod C. An excess of sodium p-toluenesulfinate was added to
a solution of 3.0 g. of impure trans trans-XI in aqueous ethanol. The
mixture was allowed to remain at room temperature for 12 days. Water
was added to the mixture, and the reaction mixture was then worked up
in the same way as in the preceding methods. Again, only starting
material was recovered.
Attempted reduction of trans-2-(p-tolylsulfonyl)-4-t-butylcyclohexa-
none (trans-IX) with diborane
Diborane was bubbled into a cooled, stirred solution of approxi-
mately 0.1 g. of trangsIX in 20 ml. of tetrahydrofuran until the infra-
red spectrum of the solution showed the disappearance of the carbonyl
absorption. The reaction mixture was heated slightly to remove the
excess diborane and then poured into water. The mixture was extracted
with ether and the ether extracts worked up in the usual way. The
solvent was removed, leaving a yellow oil as the residue. The infra-
red spectrum of the oil indicated that there was some unsaturated ma-
terial and some alcohol in the product, Attempts to produce a solid
from the oil were not too successful, yielding only a few dark colored
crystals, m.p. 106-1170. This reaction must be repeated when more of
the starting material is available.
Attempted ester interchange reaction using 2 -(p-_tolylsulfonyl)-
4c-t-butylcyclohexyl p-toluenesulfonate (trans, ci_-I tosylate)
Method A (29), To 20 ml. of glacial acetic acid containing
5.0 g. of anhydrous potassium acetate was added 4.6 g. of the trans
cis-I tosylate, and the mixture was heated on a steam bath for 24
hours. The reaction mixture was poured into 10% sodium hydroxide
and cooled before extracting with ether. The other extracts were
washed with water, and dried over sodium sulfate. The solvent was
removed, leaving an oil as the residue. The oil was taken up in
ethanol and the solution cooled. Only starting material was re-
Method B (30). To 200 ml. of glacial acetic acid containing
1.1 g. of sodium acetate was added 2.2 g. of the Irans cis-I tosy-
late, and the mixture was heated on a steam bath for 3 days. The
reaction mixture was poured into water and extracted with ether.
The ether extracts were washed with 10% sodium bicarbonate and water,
and then dried over sodium sulfate. The solvent was removed. The
infra-red spectrum of the crude product showed a very small hydroxyl
absorption along with starting material. Recrystallization from
ethanol yielded only starting material.
Reactions attempted in an effort to produce 2c -(p-tolylsulfonl)-4 -
t-butylcyclohexyl p-toluenesulfonate (cis cis-I tusylate)
Method A. p-Toluenesulfonyl chloride and the js, cis-I alcoh(
were added to dry pyridine and allowed to remain at room temperature
The reaction was set up and run for 24 hours, 7 days, 35 days, and 60
days. The reaction mixtures were worked up in the same way as the re-
action mixtures for the other tosylates. In all four cases, only the
starting alcohol was recovered. There were no indications that the
tosylate had over been formed.
Method B. This method was similar to Method A except that the
reaction mixture was heated for 2 hours on a steam bath. Again, no
tosylate was formed and only starting material was recovered.
IV, SLLU \Y
Three of the four possible racemic 2-(p-tolylsulfonyl)-4-t-
butylcyclohexanols have been prepared and characterized. 2c-(p-Tolyl-
sulfonyl)-4 -t-butylcyclohexanol has not been isolated as yet. The
acetate esters of the three racemates and the tosylate esters of two
of the racemates have also been prepared. The tosylate ester of 2c
(p-tolylsulfonyl)-4c-t-butylcyclohexanol has not been prepared. In
addition, the two possible isomers of 2-(p-tolylsulfonyl)-4-t-butyl-
cyclohesaiono have been prepared and characterized.
A mixture of 2 t(p-toluenethio)4 --t-butylcyclohexanol and
2 (p toluenethio)*5 -t-butylcyclohexanol was obtained from a reaction
ofsodium p-toluenethiol vith a mixture of cis- and trans*4-t-butyl-
cyclohexene oxide., The isomeric sulfides were not separated. The
mixture of sulfides was oxidized to the corresponding mixture of sul-
foxides in one instance, and to the corresponding mixture of sulfones
in another instance. 2t-(p-Tolylsulfinyl)-4c-t-butylcyclohexanol was
isolated from the oxidation mixture in the first cases and 2t-(p-
tolylsulfonyl)-4 -t-butylcyclohexanol was isolated from the oxidation
.mixture in. the second case. The isomeric sulfoxide and the isomeric
sulfone wore not isolated. However, 2t -(ptolylsulfonyl)*5 t*t-butyl-
cyclohexanol was prepared by the reaction of sodium p-toluenesulfin-
ate with the mixture of cis- and trans-4-t-butylcyclohexene oxide.
The second racemate, 2c-(p*tolylsulfonyl)-4c -*butylcyclohiea-
nol, Tas propard by cpinri ine 2 -(p-tolylsulfonyl)-4c-t-butylcyclo-
hexanol in an ethanol solution of sodium ethoxide. The third racemate,
2 -(p-tolylsulfonyl)-4 -t-butylcyclohexanol, was prepared by the di-
borane reduction of .cs-2-(p-tolylsulfonyl)*4-t-butylcyclohexanone.
The preparation of the fourth racemate, 2c-(p-tolylsulfonyl)-
4t t-butylcyclohemanol, was attempted by several routes, but without
success. The most promising route for the preparation of this race-
mate appears to be the diborane reduction of trans-2-(p-tolylsulfonyl)-
The cis--ketone, gij"2-*(p-tolylsulfonyl)-4-t-butylcyclohexanone,
was obtained be several methods. Among these were the reaction of
trans-2-bromo-4-t-butylcyclohexanone with sodium p-toluenesulfinate,
the oxidation of the epimer, 2c*(p-tolylsulfonyl)*4c-t*butylcyclo-
hexanol, and the oxidation of 2 -(p-tolylsulfonyl)-4c-t-butylcyclo-
hexanol. By varying the conditions and the oxidizing agent, 2-(p-
tolylsulfonyl)-4 -t-butylcyclohexanol was oxidized to the trans-ketone,
trans-2-(p-tolylsulfonyl)-4-t-butylcyclohe:anone, in one case and to
the cis-ketone, gs-2-(p-tolyloulfonyl)-4-t-butylcyclohexanone, in
another case. In a third instance, a mixture of the cis- and trans*
ketones was obtained. The pure trans-ketone was obtained by o::idiling
2 *(p-tolylsulfonyl)-4c-t-butylcyclohexanol with activated ningaense.
dioxide. An attempt was made to prepare the trans-ketone by the
reaction of cis-2-bromo-4-t-butylcyclohexanone with sodium p-toluene-
sulfinate, but this reaction was not successful. It is felt that a
good method for the preparation of the trans-kotone must be found in
order to examine the diborane reduction more closely.
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Herrill Lynn was born November 20, 1930, at New Columbia,
Pennsylvania. In June, 1948, he was graduated from Iilton HIIrshey
High School, Hershey, Pennsylvania. In June, 1950, he was graduated
from Hershey Junior College. From October, 1950 until September, 1954,
Mr. Lynn served in the U.S. Air Force. In June, 1956, he received the
degree of Bachelor of Science from Bucknell University. In September,
1956, he began graduate studies in chemistry at the University of
Florida. During his residence at the University of Florida he has
worked as a graduate assistant, a research assistant, and a teaching
assistant in the Chemistry Department. From September, 1960 until
the present time he has been self-employed.
Merrill Lynn is married to the former Lydia Ann Tiemann.
This dissertation was prepared under the direction of the
chairman of the candidate's supervisory committee and has been approved
by all meabors of that comrittce. It was submitted to the Dean of the
College of Arts and Scioenes and to the Graduate Council, and was
approved as partial fulfillment of the requirements for the dagrce of
Doctor of Philosophy.
August 12, 1961
Dean, College of Arts ar ^ences
Dean, Graduate School
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