Enthalpic and entropic contributions to the conformational free energies of methylthio, methylsulfinyl, methylsulfonyl, phenylthio, phenylsulfinyl, and phenylsulfonyl [s(o)(n)r, n = 0, 1, 2; r = ch3, ph] groups in cyclohexane

Article abstract of DOI:10.1021/jo991181u

A variable-temperature NMR study of (cis-4-methylcyclohexyl)methyl sulfide (1), sulfoxide (2), and sulfone (3), as well as (cis-4- methylcyclohexyl)phenyl sulfide (4), sulfoxide (5), and sulfone (6) allowed determination of the thermodynamic parameters, ΔH°and ΔS°, for the title groups. Reproduction of the experimental results with Allinger's MM3 program was successfully accomplished in the case of the sulfoxide and sulfide groups. Nevertheless, modification of the original force field torsional parameters was required in order to adequately reproduce the experimentally observed behavior of the sulfonyl derivatives. Rationalization of the enthalpic and entropic contributions to ΔG°[S(O)(n)R, n = 0, 1, 2; R = CH₃, Ph] is advanced in terms of the steric characteristics of these sulfurcontaining groups and the resulting rotameric populations in the axial and equatorial monosubstituted cyclohexanes.

Full text of DOI:10.1021/jo991181u

J . Org. Chem. 2000, 65, 969-973
969
En th a lp ic a n d En tr op ic Con tr ibu tion s to th e Con for m a tion a l F r ee
En er gies of Meth ylth io, Meth ylsu lfin yl, Meth ylsu lfon yl,
P h en ylth io, P h en ylsu lfin yl, a n d P h en ylsu lfon yl [S(O)n R, n ) 0, 1, 2;
R ) CH3, P h ] Gr ou p s in Cycloh exa n e
Eusebio J uaristi,* Victoria Labastida, and Sandra Antu´nez
Departamento de Quı´mica, Centro de Investigacio´n y de Estudios Avanzados del Instituto Polite´cnico
Nacional, Apartado Postal 14-740, 07000 Me´xico, D.F., Me´xico
Received J uly 26, 1999
A variable-temperature NMR study of (cis-4-methylcyclohexyl)methyl sulfide (1), sulfoxide (2), and
sulfone (3), as well as (cis-4-methylcyclohexyl)phenyl sulfide (4), sulfoxide (5), and sulfone (6) allowed
determination of the thermodynamic parameters, ∆H° and ∆S°, for the title groups. Reproduction
of the experimental results with Allinger’s MM3 program was successfully accomplished in the
case of the sulfoxide and sulfide groups. Nevertheless, modification of the original force field torsional
parameters was required in order to adequately reproduce the experimentally observed behavior
of the sulfonyl derivatives. Rationalization of the enthalpic and entropic contributions to ∆G°
[S(O)nR, n ) 0, 1, 2; R ) CH3, Ph] is advanced in terms of the steric characteristics of these sulfur-
containing groups and the resulting rotameric populations in the axial and equatorial monosub-
stituted cyclohexanes.
Ta ble 1. En th a lp ic a n d En tr op ic Con tr ibu tion s to th e
Con for m a tion a l F r ee En er gy Differ en ces (∆G°298K) of
Releva n t Alk yl Gr ou p s (eq 1)4-6
In tr od u ction
The conformational behavior of monosubstituted cy-
clohexanes is of fundamental importance in organic
chemistry since it effectively models larger and more
complex molecules.1 Alkyl groups prefer equatorial over
axial positions in order to prevent the repulsive steric
interactions with the C(3,5) methylenes (eq 1), and it is
usually observed that the bulkier the alkyl group the
larger the preference for the equatorial form.2
entry
R
∆H°
∆S°
∆G°298K
1
2
3
4
5
Me
Et
i-Pr
Bn
-1.75
-1.60
-1.52
-1.52
-5.00
-0.03
+0.64
+2.31
+0.81
-0.44
-1.74
-1.79
-2.21
-1.76
-4.87
t-Bu
Furthermore, the benzyl group exhibits similar thermo-
dynamic behavior (entry 4 in Table 1),5 whereas by
contrast, the axial isomer of tert-butylcyclohexane has
greater entropy in the axial relative to the equatorial
isomer (entry 5 in Table 1).6
The interesting observations described in the previous
paragraph have been well discussed in the literature3-6
and provide convincing evidence that a proper under-
standing of conformational behavior is viable only with
adequate knowledge of the enthalpic and entropic con-
tributions to ∆G°. Indeed, such dissection of conforma-
tional energies into ∆H° and ∆S° components has been
essential for interpretation of the conformational behav-
ior of various substituted heterocycles.7-10
In this context, force-field calculations3 and experi-
mental NMR data4 showed that while the conformational
free energy differences (∆G° values) increase along the
series methyl f ethyl f isopropyl, the enthalpic contri-
butions to the equatorial preference actually decrease
along this series (entries 1-3 in Table 1), so that it is
the T∆S° term that accounts for the observed trend.
* To whom correspondence should be addressed. E-mail: juaristi@
relaq.mx.
Two decades ago, Eliel and Kandasamy determined the
conformational energies of the methylthio, methylsulfi-
nyl, and methylsulfonyl groups by low-temperature 13C
(1) (a) Barton, D. H. R. Experientia 1950, 6, 316. (b) Winstein, S.;
Holness, N. J . J . Am. Chem. Soc. 1955, 77, 5562. (c) Eliel, E. L.;
Allinger, N. L.; Angyal, S. J .; Morrison, G. A. Conformational Analysis;
Interscience: New York, 1965. (d) J uaristi, E. Introduction to Stere-
ochemistry and Conformational Analysis; Wiley: New York, 1991. (e)
J uaristi, E., Ed. Conformational Behavior of Six-Membered Rings:
Analysis, Dynamics, and Stereoelectronic Effects; VCH Publishers:
New York, 1995.
(2) (a) Hirsch, J . A. Top Stereochem. 1967, 1, 199. (b) Bushweller,
C. H. Stereodynamics of Cyclohexane and Substituted Cyclohexanes.
Substituent A-Values; Chapter 2 in ref 1e.
(3) Allinger, N. L.; Hirsch, J . A.; Miller, M. A.; Tyminski, I. J .; Van-
Catledge, F. A. J . Am. Chem. Soc. 1968, 90, 1199.
(5) J uaristi, E.; Labastida, V.; Antu´nez, S. J . Org. Chem. 1991, 56,
4802.
(6) Antu´nez, S.; J uaristi, E. J . Org. Chem. 1996, 61, 6465.
(7) Bailey, W. F.; Connon, H.; Eliel, E. L.; Wiberg, K. B. J . Am.
Chem. Soc. 1978, 100, 2202.
(8) (a) Booth, H.; Grindley, T. B.; Khedhair, K. A. J . Chem. Soc.,
Chem. Commun. 1982, 1047 (b) Booth, H.; Readshaw, S. A. Tetrahe-
dron 1990, 46, 2097. (c) Booth, H.; Dixon, J . M.; Readshaw, S. A.
Tetrahedron 1992, 48, 6151.
(4) (a) Booth, H.; Everett, J . R., J . Chem. Soc., Perkin Trans. 2 1980,
255. (b) See, also: Wiberg, K. B.; Hammer, J . D.; Castejon, H.; Bailey,
W. F.; DeLeon, E. L.; J arret, R. M. J . Org. Chem. 1999, 64, 2085. (c)
See, also: Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry of
Organic Compounds; J ohn Wiley & Sons: New York, 1994.
(9) (a) J uaristi, E.; Gonza´lez, E. A.; Pinto, B. M.; J ohnston, B. D.;
Nagelkerke, R. J . Am. Chem. Soc. 1989, 111, 6745. (b) J uaristi, E. Acc.
Chem. Res. 1989, 22, 357.
(10) (a) J uaristi, E.; Cuevas, G. Tetrahedron Lett. 1992, 33, 2271.
(b) J uaristi, E.; Cuevas, G. J . Am. Chem. Soc. 1993, 115, 1313.
10.1021/jo991181u CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/02/2000

970 J . Org. Chem., Vol. 65, No. 4, 2000
J uaristi et al.
Sch em e 1
NMR signal area measurements.11 The single-tempera-
ture -∆G°178K values obtained in this work were antici-
pated to become more negative at higher temperature
owing to entropy effects. In particular, three populated
rotamers in the equatorial isomers versus one [CH3S-
(O)] or two [CH3S, CH3SO2] populated rotamers in the
axial form12 imply that the entropy of mixing should
make a substantial contribution to the free energy
difference.
The present paper reports the results of variable-
temperature 13C NMR measurements in (cis-4-methyl-
cyclohexyl)methyl sulfide, sulfoxide, and sulfone (1-3),
as well as in the SC6H5 analogues 4-6, which permitted
the determination of ∆H° and ∆S° in axial to equatorial
equilibria (Scheme 1). The cis-methyl at C(4) serves as a
counterpoise substituent,11,13 so that equilibrium con-
stants, K, are closer to unity.
F igu r e 1. ln K as a function of 1/T for 1-6.
Ta ble 3. Va r ia ble-Tem p er a tu r e Con for m a tion a l
Equ ilibr iu m Con sta n ts of Com p ou n d s 1-6 (Sch em e 1) in
CDCl3
temp,
K
∆G°,
kcal/mol compd
temp,
K
∆G°,
compd
K
K
kcal/mol
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
4
313 0.409
300 0.383
288 0.372
273 0.341
258 0.322
313 0.728
300 0.696
288 0.665
273 0.621
258 0.579
0.556
0.572
0.566
0.583
0.581
0.197
0.216
0.233
0.258
0.280
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
6
300 0.352
288 0.337
273 0.312
258 0.289
183 0.166
313 1.06
300 1.03
288 0.98
273 0.94
258 0.89
313 0.195 -1.017
303 0.192 -0.944
273 0.174 -0.949
243 0.154 -0.903
223 0.143 -0.862
183 0.113 -0.793
0.622
0.622
0.631
0.636
0.653
-0.036
-0.018
-0.012
-0.034
-0.060
Resu lts
A. Syn th etic a n d Sp ectr oscop ic P a r t. trans-4-
Methylcyclohexyl mesylate (7) was prepared from trans-
4-methylcyclohexanol14 according to the usual procedure15
and reacted with sodium thiomethoxide (CH3S-Na+) to
give cis-1, or with sodium thiophenoxide (C6H5S-Na+) to
give cis-4. Oxidation of cis-1 and cis-4 with 1 equiv of
sodium periodate afforded sulfoxides cis-2 and cis-5,
respectively, whereas treatment of cis-1 with excess
hydrogen peroxide gave sulfones cis-3 and cis-6, respec-
tively (Scheme 2).
313 3.677 -0.810
300 3.491 -0.825
288 4.280 -0.832
273 4.604 -0.828
258 5.067 -0.832
313 0.384
0.605
Ta ble 4. Th er m od yn a m ic P a r a m eter s for 1-6
Application of Eliel’s equation16 [K ) (δeq - δmobile)/
(δmobile - δax)] to the variable temperature 13C NMR data17
(Table 2, Supporting Information) affords the equilibrium
constants listed in Table 3. Plots of ln K versus 1/T
(Figure 1) show good correlations, and the thermody-
namic parameters derived from linear regression are
listed in Table 4. Consideration of the thermodynamic
parameters of the counterpoise substituent, ∆H°(CH3) )
-1.75 kcal/mol and ∆S°(CH3) ) -0.03 cal/K‚mol,4a gives
the data collected in Table 5.
X
∆H° (kcal/mol)
∆S° (cal/°K‚mol)
CH3S
+0.70 ( 0.09
+0.67 ( 0.06
-0.91 ( 0.09
+0.71 ( 0.11
+0.53 ( 0.06
-0.49 ( 0.10
+0.45 ( 0.31
+1.52 ( 0.30
-0.28 ( 0.30
+0.31( 0.38
+1.76( 0.15
+1.66 ( 0.26
CH3S(O)
CH3SO2
PhS
PhS(O)
PhSO2
Discu ssion
of the experimentally derived enthalpy and entropy terms
into equation ∆G° ) ∆H° - T∆S°. Comparison of these
values with those reported by Eliel11 for 1-3 shows
excellent agreement. Indeed, for the series CH3S, CH3S(O),
and CH3SO2, we obtain ∆G°178K ) -1.14, -1.36, -2.61
kcal/mol, respectively, to be compared with Eliel and
Kandasamy’s -1.00, -1.20, and -2.50 kcal/mol, respec-
tively.11
With respect to enthalpy terms, the similarity among
those obtained for the methylthio and methylsulfinyl
groups (∆H° ) -1.05 and -1.08 kcal/mol, respectively)
is in line with expectation (see above) that a sulfur lone
pair confronts the ring in both these systems. On the
other hand, the more than double ∆H° term for CH3SO2,
-2.66 kcal/mol, reflects the additional steric repulsion
caused by the oxygen-inside interaction in the axial
sulfone, worth ca. 1.6 kcal/mol. A similar trend is found
Table 5 includes the conformational free energy dif-
ferences at 298 K and 178 K, estimated by incorporation
(11) Eliel, E. L.; Kandasamy, D. J . Org. Chem. 1976, 41, 3899.
(12) The methyl-inside rotamer of axial methylthio- and methyl-
sulfonylcyclohexane is nearly 3 kcal/mol higher in energy and can be
disregarded. The oxygen-inside rotamer of axial methylsulfinylcyclo-
hexane is nearly 1.5 kcal/mol higher in energy,11 thus the axial
sulfoxide exists largely (over 90%) with the sulfur lone pair pointing
inside the ring.
(13) Eliel, E. L.; Della, E. W.; Williams, T. H. Tetrahedron Lett. 1963,
831.
(14) Obtained by Birch reduction of 4-methylcyclohexanone: Huff-
man, J . W.; Charles, J . T. J . Am. Chem. Soc. 1968, 90, 6486.
(15) Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis;
Wiley: New York, 1967; Vol. 1, pp 1179-1181.
(16) Eliel, E. L. Chem. Ind. (London) 1959, 568.
(17) CH3-C(4) provides the most adequate spread (δeq - δax) of
chemical shifts to make such a calculation reliable. The shifts δeq and
δax were determined by measurement below coalescence temperature
(assuming linear temperature dependence).

Enthalpic and Entropic Contributions
J . Org. Chem., Vol. 65, No. 4, 2000 971
Sch em e 2
Ta ble 5. Th er m od yn a m ic P a r a m eter s for th e
Meth ylth io, Meth ylsu lfin yl, Meth ylsu lfon yl, P h en ylth io,
P h en ylsu lfin yl, a n d P h en ylsu lfon yl Gr ou p s in
Cycloh exa n e
K‚mol (Table 5, entry 3), although small, is contrary to
that anticipated based on steric terms.11 Nevertheless,
the corresponding value for the C6H5SO2 group, ∆S° )
+1.66 cal/K‚mol (Table 5, entry 6) seems congruent with
expectation.
B. Molecu la r Mech a n ics Ca lcu la tion s. The MM3-
(94)18 force field was used to evaluate the intramolecular
energetics for equilibria 8-13-ax h 8-13-eq. Uniform
scanning at 5° increments was carried out for the θ1 and
θ2 dihedral angles (eq 2), allowing for complete relaxation
of the rest of the atomic coordinates. The conformational
energy plots originating from each minimum energy
conformation were drawn by means of the Surfer pro-
gram.19
c
c
∆H°,a
∆S°,b
∆G°298K
,
∆G°178K,
entry
X
kcal/mol
cal/K‚mol
kcal/mol kcal/mol
1
2
3
4
5
6
CH3S
-1.05 ( 0.09 +0.48 ( 0.31
CH3S(O) -1.08 ( 0.06 +1.55 ( 0.30
-2.66 ( 0.09 -0.26 ( 0.30
-1.04 ( 0.11 +0.32 ( 0.38
C6H5S(O) -1.22 ( 0.06 +1.82 ( 0.15
C6H5SO2 -2.44 ( 0.10 +1.66 ( 0.26
-1.19
-1.54
-2.58
-1.12
-1.76
-2.94
-1.14
-1.36
-2.61
-1.10
-1.54
-2.74
CH3SO2
C6H5S
a
Negative values indicate that the equatorial conformer is
favored enthalpically. b Positive values indicate that the equatorial
conformer is favored entropically. c Negative values indicate that
the equilibrium is shifted to the equatorial isomer.
Sch em e 3
The free-space intramolecular entropy20 was calculated
according to eq 3 where R is the gas constant, n is the
number of conformational states sampled, and Pi is the
Boltzmann probability in the ith conformational state.
n
Sγ ) - R P ln P
(3)
∑
i
i
i)1
in the phenyl analogues, with ∆H° ) -1.04 and -1.22
kcal/mol for the sulfide and sulfoxide, respectively, and
then a substantial ∆H° ) -2.24 kcal/mol for the sulfone
derivative (Table 5, entries 4, 5, and 6).
The Pi, in turn, were computed from the relationship
e-E /RT
i
Pi )
(4)
n
The entropy data obtained in the present work is also
congruent with expectation in the cases of the sulfide and
sulfoxide groups. As discussed in the Introduction, two
populated rotamers of axial methylthio group versus
three in the equatorial isomer (Scheme 3) suggests an
entropy of mixing approaching R ln 3 - R ln 2 ) 0.80
cal/K‚mol (experimental, ∆S° ) +0.48 cal/K‚mol). In the
case of the methylsulfinyl group, only one axial rotamer
indicates a maximum value for ∆S° mixing ) R ln 3 - R
ln 1 ) 2.18 cal/K‚mol (experimental, ∆S° ) + 1.55 cal/
K‚mol). Again, this trend is reproduced in the C6H5S/
C6H5S(O) series, with ∆S° values of +0.32 and +1.82 cal/
K‚mol, respectively.
e-E /RT
i
∑
i)1
where Ei is the intramolecular conformational energy of
the ith state.
Table 6 presents the calculated thermodynamic data
for equilibria 1-6-ax h 1-6-eq and includes the corre-
sponding experimental values for comparison purposes.
The agreement between experiment and MM3 is good for
(18) Allinger, N. L.; Yuh, Y. H.; Lii, J . H. J . Am. Chem. Soc. 1989,
111, 8551.
(19) Surfer version 4.0, Golden Software, Inc., 809 14th St., P.O.
Box 281, Golden, CO 80402-0281.
(20) Flory, P. J . Statistical Mechanics of Chain Molecules; Wiley:
New York, 1969. See also: Lo´pez de Compadre, R. L.; Pearlstein, R.
A.; Hopfinger, A. J .; Seydel, J . K. J . Med. Chem. 1987, 30, 900.
With regard to the sulfonyl groups, the experimentally
observed negative ∆S° value for the axial to equatorial
conversion of the methylsulfonyl group, ∆S° ) -0.29 cal/

972 J . Org. Chem., Vol. 65, No. 4, 2000
J uaristi et al.
Ta ble 6. Com p a r ison of Exp er im en ta l (th is w or k ) a n d
Ca lcu la ted [MM3(94) F or ce F ield , E ) 8.9].
Th er m od yn a m ic Da ta for 8-13-a x h 8-13-eq
R
∆H°exptl
∆S°exptl
∆H°MM3
∆S°MM3
SCH3
-1.05
-1.08
-2.66
-1.04
-1.22
-2.24
+0.46
+1.53
-0.28
+0.32
+1.82
+1.66
-1.51
-1.05
-0.66
-1.45
-0.99
-0.70
+0.61
+0.90
+0.40
+0.16
+0.90
+0.16
S(O)CH3
SO2CH3
SC6H5
S(O)C6H5
SO2C6H5
Ta ble 7. Revised Tor sion a l P a r a m eter s for th e
Csp 3-Csp 3-Csp 3-SO2 Segm en t, in k ca l/m ol
segment
V1
V2
V3
C-C-C-SO2
-0.394
0.0
-0.368
F igu r e 2. Population surfaces for axial (top) and equatorial
(bottom) S-methyl group rotation in cyclohexane.
sulfides and sulfoxides, but for sulfones the agreement
is poor. The possibility was considered that solvation by
hydrogen bonding solvents such as chloroform or meth-
ylene chloride could be responsible for the discrepancy
in the case of the sulfonyl derivatives, but then it seems
odd that sulfoxides should not be affected too by solvation
effects not taken into account in the force field. Further-
more, MM3 calculations did not reproduce the energy
barriers calculated for rotation around the CH3CH2-CH2-
SO2CH3 bond by means of ab initio methods.21
As it turns out,22 sulfide and sulfoxide force field
parameters were determined with the aid of Hartree-
Fock calculations which contained polarization functions,
but the sulfone parameters were obtained from ab initio
calculations which did not include polarization functions,
rendering the results highly suspect. Indeed, examination
of the various parameters contributing to the steric
energy calculated in the force field revealed anomalous
3
values for the estimated torsional energies in Csp3-Csp
-
Csp3-S(O)n segments. Thus, reparametrization was car-
ried out by systematic modification of the V1 and V3
torsion parameters, maintaining V2 ) 0 and V1:V3 ) 1.5:
1.4, until the calculation matched the experimentally
observed ∆H° values. Table 7 presents the revised
torsional parameters for the Csp3-Csp3-Csp3-SO2 seg-
ment.
F igu r e 3. Population surfaces for axial (top) and equatorial
(bottom) S-phenyl group rotation in cyclohexane.
anol14 according to the usual procedure15) in 4 mL of ethanol,
and the reaction mixture was heated to reflux for 4 h and
stirred at ambient temperature for 55 h. Extraction with CH2-
Cl2 and the usual workup procedure afforded 0.09 g (24.0%
yield) of cis-1 as a yellowish oil. 1H and 13C NMR spectra were
essentially identical to those reported in the literature.11
(cis-4-Meth ylcycloh exyl)m eth yl Su lfoxid e (cis-2). cis-1
(0.22 g, 1.52 mmol) was oxidized with sodium periodate (0.34
g, 1.58 mmol) following the literature procedure, to give 0.18
g (74.4% yield) of cis-2 as a hygroscopic solid, mp 60-61 °C
(lit.11 58-59 °C). 1H and 13C NMR spectra were essentially
identical to those reported.11
(cis-4-Meth ylcycloh exyl)m eth yl Su lfon e (cis-3). The
procedure used was similar to that of Eliel and Kandasamy,11
with 0.24 g (1.66 mmol) of cis-1, to obtain 0.25 g (85.2% yield)
of the desired product, whose 1H and 13C NMR data were
similar to those reported.11
Inclusion of the new parameters collected in Table 7
did reproduce the energy barriers for rotation in the
model, CH3CH2-CH2SO2CH3, as estimated by ab initio
methods.
Figures 2-7 present the Boltzmann populations in
axial and equatorial 8-13.
Exp er im en ta l Section
Gen er a l In for m a tion . 13C NMR (67.5 MHz) spectra were
recorded on a 270 MHz spectrometer. Chemical shifts are given
in parts per million downfield from TMS (δ). The probe
thermocouple was used for temperature measurement, after
calibration. Temperatures are believed to be accurate to within
(2 K.
(cis-4-Meth ylcycloh exyl)m eth yl Su lfid e (cis-1). Sodium
thiomethoxide (0.18 g, 2.60 mmol) in 10 mL of ethanol was
treated with 0.5 g (2.60 mmol) of trans-4-methylcyclohexyl
methanesulfonate (7, prepared from trans-4-methylcyclohex-
(cis-4-Meth ylcycloh exyl)p h en yl Su lfid e (cis-4). In a 50-
mL round-bottom flask was placed an ethanolic solution of
sodium ethoxide (0.1 g, 4.34 mmol of sodium in 10 mL of
ethanol), and to this was added dropwise a solution of 0.3 mL
(2.92 mmol) of thiophenol in 1.0 mL of ethanol. The resulting
thiophenoxide solution was treated with 0.5 g (2.60 mmol) of
mesylate 7 dissolved in 4.0 mL of ethanol, and the reaction
mixture was heated to reflux for 60 h. Extraction with CH2-
(21) The ab initio calculations were done with Gamess(US) 6-31G**,
with inclusion of electron correlation.
(22) Allinger, N. L., personal communication.

Enthalpic and Entropic Contributions
J . Org. Chem., Vol. 65, No. 4, 2000 973
F igu r e 6. Population surfaces for axial (top) and equatorial
(bottom) methylsulfonyl group rotation in cyclohexane.
F igu r e 4. Population surfaces for axial (top) and equatorial
(bottom) methylsulfinyl group rotation in cyclohexane.
F igu r e 7. Population surfaces for axial (top) and equatorial
(bottom) phenylsulfonyl group rotation in cyclohexane.
F igu r e 5. Population surfaces for axial (top) and equatorial
30% aqueous H2O2 was stirred at ambient temperature for 3
h. The reaction mixture was diluted with 14.0 mL of water
and extracted with CH2Cl2. The organic phase was washed
with saturated aqueous NaHCO3 and water, dried with Na2-
SO4, and concentrated in the rotary evaporator to give 0.19 g
(81.1% yield) of cis-6 as a white solid that was recrystallized
from hexane, mp 63-64 °C. 1H NMR (CDCl3, 270 MHz) δ 0.91
(d, J ) 7.2 Hz, 3 H), 1.41-1.93 (m, 9 H), 2.91 (m, 1 H), 7.5-
7.88 (m, 5 H). 13C NMR (CD2Cl2, 270 MHz) δ 18.2, 21.1, 27.7,
30.6, 63.0, 129.2, 129.5, 133.9, 138.3. Anal. Calcd for
(bottom) phenylsulfinyl group rotation in cyclohexane.
Cl2 was followed by neutralization with aqueous 10% KOH.
The usual workup procedure afforded 0.52 g (97% yield) of cis-
4. 1H NMR (CDCl3, 270 MHz) δ 0.93 (d, J ) 5.9 Hz, 3 H), 1.42-
1.86 (m, 9 H), 3.47 (m, 1 H), 7.14-7.4 (m, 5 H). 13C NMR
(CD2Cl2, 67.5 MHz) δ 21.6, 30.3, 31.6, 45.6, 126.5, 129.0, 131.4,
136.6. Anal. Calcd for C13H18S: C, 75.67; H, 8.79. Found: C,
75.87; H, 8.72.
(cis-4-Meth ylcycloh exyl)p h en yl Su lfoxid e (cis-5). In a
25-mL round-bottom flask was placed 0.2 g (0.97 mmol) of
sulfide cis-4, 3.0 mL of CH2Cl2, and 10 mL of CH3OH. This
solution was cooled to 0 °C before the slow addition of 0.23 g
(1.07 mmol) of NaIO4 dissolved in 2.5 mL of water. The
resulting reaction mixture was stirred for 8 h at 0 °C and then
left standing in the refrigerator for 24 h. The usual workup
procedure afforded 0.17 g (79% yield) of the desired product,
C
13H18O2S: C, 65.51; H, 7.61. Found: C, 65.36; H, 7.63.
Su p p or tin g In for m a tion Ava ila ble: Variable-tempera-
ture 13C NMR chemical shifts of cis-1-3. This material is
available free of charge via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. We are grateful to Profs. E. L.
Eliel and N. L. Allinger for useful comments, to CONA-
CYT (project L0006-E) for financial support, and to G.
Uribe for recording the variable-temperature NMR
spectra. We are also indebted to Fred Garc´ıa, Omar
Mun˜oz-Mun˜iz, and Marcos Herna´ndez-Rodr´ıguez for
technical assistance.
1
cis-5, as a colorless oil. H NMR (CDCl3, 270 MHz) δ 0.96 (d,
J ) 6.6 Hz, 3 H), 1.39-1.81 (m, 9 H), 2.20 (m, 1 H), 7.50.-7.67
(m, 5 H). 13C NMR (CD2Cl2, 67.5 MHz) δ 20.2, 22.1, 24.0, 30.8,
30.8, 31.4, 64.0, 125.5, 129.3, 131.4, 143.9.
(cis-4-Meth ylcycloh exyl)p h en yl Su lfon e (cis-6). A solu-
tion containing 0.2 g (9.7 mmol) of sulfide cis-4, 4.0 mL of a
1:1 mixture of acetic anhydride and acetic acid, and 1.4 mL of
J O991181U