Oxidative transformations of diisobornyl disulfide

Article abstract of DOI:10.1007/s11172-014-0702-8

Oxidation of diisobornyl disulfide with m-chloroperoxybenzoic acid, lead tetracetate, and chlorine dioxide was studied. Depending on the reaction conditions, the following products with the increasing oxidation number of the sulfur atom were obtained: diisobornyl trisulfide, isobornyl isobornanethiosulfinate, isobornanesulfinyl chloride, isobornanesulfinic, isobornanesulfonic acid and their esters.

Full text of DOI:10.1007/s11172-014-0702-8

Russian Chemical Bulletin, International Edition, Vol. 63, No. 9, pp. 2067—2073, September, 2014
2067
Oxidative transformations of diisobornyl disulfide*
E. S. Izmest´ev, O. M. Lezina, O. N. Grebyonkina, S. A. Patov, S. A. Rubtsova, and A. V. Kutchin
Institute of Chemistry, Komi Scientific Center, Ural Branch of the Russian Academy of Sciences,
48 ul. Pervomaiskaya, 167982 Syktyvkar, Russian Federation.
Fax: +7 (821) 221 8477. Eꢀmail: izmestevꢀes@chemi.komisc.ru
Oxidation of diisobornyl disulfide with mꢀchloroperoxybenzoic acid, lead tetracetate, and
chlorine dioxide was studied. Depending on the reaction conditions, the following products
with the increasing oxidation number of the sulfur atom were obtained: diisobornyl trisulfide,
isobornyl isobornanethiosulfinate, isobornanesulfinyl chloride, isobornanesulfinic, isobornaneꢀ
sulfonic acid and their esters.
Key words: diisobornyl disulfide, oxidation, chlorine dioxide, sulfinic esters, sulfonic esters,
sulfinyl chlorides, disulfides, trisulfides, tetrasulfides, terpenoids.
Studies on oxidation of terpene thiols and terpene diꢀ
sulfides are of great interest since they provide an open
access to the oxygenꢀcontaining terpene derivatives wideꢀ
ly used for asymmetric synthesis of novel compounds.1
Among thiol derivatives applied for asymmetric synthesis,
sulfinyl chlorides are most known;2—4 however, terpene
sulfinyl chlorides have not been synthesized to date due to
high lability of the terpene moiety and instability of these
compounds. Sulfonic acids and their esters are other imꢀ
portant class of compounds having numerous applications
in organic synthesis and pharmaceutical industry, e.g., for
the synthesis of sulfocamphocaine, semiꢀsynthetic peniꢀ
cillins, and cephalosporins.5 Up to the present time, synꢀ
thesis of oxygenꢀcontaining derivatives of terpene thiols
are scarcely studied despite very promising synthetic poꢀ
tential of these compounds.
In the present work, we first performed comparative
studies of the oxidation of diisobornyl disulfide 1 with
mꢀchloroperoxybenzoic acid (MCPBA), lead tetraacetate
(Pb(OAc)4), and chlorine dioxide (ClO2) with the aim to
find a new synthetic potential of these oxidants, establish
the features of the reactions and the possibility of the seꢀ
lective oxidation of terpene disulfide.
most extensively studied.9 Chlorine dioxide was successꢀ
fully used in the synthesis of dialkyl and diaryl thiosulꢀ
fonates, sulfonic acids, and sulfonyl chlorides.10—12 In the
present work, we first performed oxidation of terpene diꢀ
sulfide with Pb(OAc)4 and ClO2; earlier we used MCPBA
for oxidation of terpene disulfides bearing menthane and
neomenthane moieties.13
Oxidation of disulfide 1 with 1 equiv. of MCPBA in
CHCl3 or CH2Cl2 gives diastereomeric thiosulfinate 2 in
quantitative yield (Scheme 1). Compound 2 is stable only
in solution and readily decomposes upon solvent removal.
The attempts to isolate thiosulfinate 2 by silica gel column
chromatography failed owing to complete decomposition
of 2. The main decomposition products are the starting
disulfide 1, formed via disproportionation (see Scheme 1,
route i) characteristic for all thiosulfinates, and thiocamꢀ
phor 3, arising from elimination (see Scheme 1, route ii)
characteristic of cyclic thiosulfinates. Apparently, these
reactions are also give rise to thiosulfonate 4 and isoborꢀ
nanesulfenic acid 5.14,15
Thiosulfinate 2 was isolated as a diastereomeric mixꢀ
ture (de 35%) by neutral Al2O3 column chromatography
and the structures of diastereomers were studied by NMR
and IR spectroscopy. IR spectrum diastereomers 2 exhibꢀ
it intensive bands of the S=O stretching vibrations at
Results and Discussion
1
1076 cm–1. In H spectrum, the protons of the isobornyl
moieties bonded to the sulfanyl and sulfinyl groups resoꢀ
nate, respectively, at  3.23 and 3.48 for the major isomer
and at  3.13 and 3.39 for the minor isomer. In 13C NMR
spectrum, two diastereomeric thiosulfinates 2 appear also
as two sets of the signals ascribed to nonꢀequivalent
isobornyl fragments.
It is known that MCPBA oxidation of disulfides in low
polar aprotic solvents leads to products with increasing
oxidation states, namely, thiosulfinates, thiosulfonates,
and sulfonic acids.6—8 Oxidation of aromatic disulfides
with Pb(OAc)4 in alcohols resulting in sulfinic esters is
It is known that due to low stability, thiosufinates can
react with alcohols following nucleophilic substitution
mechanism to give more stable sulfinic esters.16 Adding
* Based on the materials of the VIII AllꢀRussian Conference
"Chemistry and Technology of Plant Substances" (October, 7—10,
2013, Kaliningrad).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2067—2073, September, 2014.
1066ꢀ5285/14/6309ꢀ2067 © 2014 Springer Science+Business Media, Inc.

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Izmest´ev et al.
Scheme 1
i. Disproportionation, ii. Elimination.
MeOH to a solution of thiosulfinate 2 does not produce
the corresponding ester; however, refluxing the reaction
mixture for 3—4 h in the presence of BF3•Et2O surprisꢀ
ingly gives tetrasulfide 6 in 70% yield and ether 7 (see
Scheme 1). Formation of tetrasulfides by thermal decomꢀ
position of thiosulfinates was previously described,14
though up to present there are no unambiguous data on
mechanism of this reaction.
Structure of tetrasulfide 6 was determined by IR and
NMR spectroscopy and mass spectrometry and confirmed
by elemental analysis data. IR spectra of tetrasulfide 6 and
disulfide 1 are identical due to the absence of the functionꢀ
al groups with strong absorptions. In 1H NMR spectrum,
the H(2) signal of tetrasulfide 6 is shifted to the lower field
as compared to disulfide 1 (from  2.95 to 3.35). No noꢀ
ticeable differences in the 13C NMR spectral patterns for
compounds 1 and 6 are observed; only insignificant up
field shift of the C(2) signal of tetrasulfide 6 ( 64.0) relaꢀ
tive to the analogous signal of disulfide 1 ( 64.8) can be
mentioned.
Attempt to perform oxidation of disulfide 1 with inꢀ
creased amount of MCPBA (up to 4 equiv.) results in
desulfurization of 1 to produce camphor.
Oxidation of disulfide 1 with ClO2 gives the following
main products: diisobornyl trisulfide (8), isobornanesulfiꢀ
nyl chloride (9), isobornanesulfonic acid (10), sulfinic and
sulfonic esters 11—15, and 2,10ꢀdichloride 16 (Scheme 2).
Solvent, reactant molar ratio, and the order of the reacꢀ
tant mixing affect the structure of the products and their
yields. Heptane, CH2Cl2, alcohols, and pyridine (waterꢀ
free and with addition of water) were used as the solvents.
Earlier,17 we found that the order of the reactant mixing
affected the structure of the products formed upon ClO2
oxidation of 1ꢀmethylꢀ2ꢀsulfanylimidazole. In the present
Scheme 2
MCPBA
R = Me (11); Et (12, 14); But (13, 15)

Oxidation of diisobornyl disulfide
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 9, September, 2014
2069
work, we also used two orders of the reactant mixing. In
the first case, the gaseous ClO2 was fed by doses into
a solution of disulfide 1 (oxidation with a lack of the oxiꢀ
dizer, method A); in the second case, a solution of disulꢀ
fide 1 was added by doses to a solution of ClO2 (oxidation
with an excess of oxidizer, method B).
In contrast to MCPBAꢀmediated oxidation, no thioꢀ
sulfinates were found upon oxidation of 1 with ClO2 in
CH2Cl2. The main product of oxidation of disulfide 1 with
2ꢀfold excess of aqueous ClO2 in CH2Cl2 is a mixture of
diastereomeric isobornanesulfinyl chlorides 9 (de 47%)
with the content in the reaction mixture up to 75% (see
Scheme 2). In 13C NMR spectrum of compound 9, the
C(2) signals lie in the lower field ( 82.7, 82.4) relative to
the C(2) signal of disulfide 1 ( 64.7). Since attempts to
isolate sulfinyl chlorides 9 by SiO2 and Al2O3 column chroꢀ
matography lead to their decomposition, we synthesized
more stable diastereomeric sulfinamides 17 in 53% total
yield (de 10%) by the reaction of 9 with Et2NH. The strucꢀ
ture of sulfinamides 17 was confirmed by the counter synꢀ
thesis (see Scheme 2). Isobornane thiol 18 reacts with
Et2NH in the presence of NCS to give sulfenamide 19,
which further is oxidized with MCPBA (1 mol) to yield
compound 17 (de 26%). As compared to compound 9,
13C NMR spectrum of sulfonamide 17 exhibits a strong
field shift of the C(2) signals (cf.  73.1, 68.7 for 17 and
 82.7, 82.3 for 9) and also signals for the ethyl groups of
the diethylamine moiety at  14.6 (Me) and  41.5 (CH2).
The NOESY NMR experiments revealed the retention of
the isobornyl moiety in the structure of compounds 9 and 17.
As mentioned above, the MCPBAꢀmediated oxidation
of disulfide 1 in MeOH does not produce isobornaneꢀ
sulfinic esters. In contrast to this result, oxidation of 1
with the ClO2 excess in MeOH proceeds with full converꢀ
sion of the substrate to afford a mixture of two diastereoꢀ
meric methyl 2ꢀisobornylsulfinates 11 (in equimolar
amounts) and sulfonic acid 10.
It was found that oxidation of disulfide 1 in the solꢀ
vents mentioned above with 0.7 equiv. of ClO2 following
method A yields trisulfide 8 (see Scheme 2). This reaction
direction is not typical for the oxidation of dialkyl and
diaryl sulfides and is favored in nonꢀpolar solvent. In hepꢀ
tane, the yield of compound 8 is 78%. It is known18,19 that
the formation of a radical cation is the first step of ClO2
oxidation of disulfides (Scheme 3). Further fragmentation
of the radical cation gives a sulfenium cation, RS+, and
an RS• radical. The sulfenium cation reacts with another
disulfide molecule to form an intermediate trisulfide
cation TC. Through the action of nucleophile, e.g.,
ClO2–, the R—S bond of intermediate TC breaks to proꢀ
vide trisulfide 8 and unstable compound of the chlorite
type, ROClO. The RS• radicals dimerize to give a new
disulfide molecule.
Scheme 3
For ClO2 oxidation of disulfide 1, EtOH and BuiOH
were also tested as the solvents. Depending on the molar
reactant ratio, the corresponding sulfinic (12, 13) or sulꢀ
fonic (14, 15) esters were obtained. NMR spectra of sulfinꢀ
ic esters 12 and 13 contain two sets of the signals for the
isobornyl and alkoxy groups indicating the presence of
two diastereomers. The C(2) atoms of diastereomers 12
and 13 resonate in lower field ( 75.2, 74.2 for 12 and
 75.5, 75.6 for 13) as compared with the C(2) signal of
the disulfide 1 ( 64.7). Apparently, esters 11—13 are the
products of the replacement of the Cl atom in compound
9 by the RO group (R = Me, Et, Bui) (see Scheme 2).
Further oxidation of sulfinates 12, 13 with the ClO2
excess affords sulfonates 14 and 15 in high yields (65—85%).
Esters 14 and 15 are the C10H17SO2OR•ROH solvates
with the apparent strong Hꢀbonding between the moleꢀ
cules. NMR spectra of these compounds exhibit the
isobornyl group signals and two sets of the alkoxy group
signals, which differ in the chemical shifts with the inteꢀ
gral intensity ratio of 1 : 1 (1H NMR data). Thus, in
13C NMR spectrum of ester 14, the carbon atom signal of
the OCH2CH3 fragment covalently bonded to the oxygen
atom is shifted downfield ( 65.8) in respect to the signal
of the analogous atom of the alcohol ( 59.0) bound to the
Mass spectrum of trisulfide 8 reveals the molecular ion
peak with m/z 370. IR spectra of compound 8 and disulꢀ
fide 1 are similar. In 13C NMR spectrum of trisulfide 8,
the C(2) signal is shifted to the higher fields ( 63.2) as
compared to the C(2) signal of disulfide 1 ( 64.8).
1H NMR spectrum of trisulfide 8 exhibits a low field shift
of the H(1) proton ( 3.19) in respect of the same signal of
disulfide 1 ( 2.95). Retention of the isobornyl skeleton is
shown by the 2D NMR techniques (HSQC, COSY, NOESY,
and HMBC). Elemental analysis data confirm the trisulꢀ
fide composition.

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Izmest´ev et al.
pellets. Melting points were determined with a Gallencampꢀ
Sanyo apparatus. 1H and 13C NMR spectra were run on a Bruker
Avanceꢀ300 instrument (working frequencies of 300.17 and
75.48 MHz, respectively) in CDCl3, the chemical shifts are givꢀ
en in the  scale relative to the residual solvent signals as internal
standard. The signals in the 1H and 13C NMR spectra were
ascribed using 2D homonuclear (1H—1H COSY, 1H—1H NOESY)
and heteronuclear (1H—13C HSQC, HMBC) NMR experiments.
Enantiomeric excesses were calculated from 1H NMR data based
on the integral intensity ratio of the signals of the protons at the
second carbon atom of the sulfinyl group. Mass spectra were
recorded using the LC/MS system comprising a high perforꢀ
mance liquid chromatograph and a Thermo Finnigan LCQ Fleet
ion trap mass spectrometer operating on the positive ion mode.
Optical rotations were measured on an automatic digital polaꢀ
rimeter Krüss P3002RS. Thin layer chromatography was perꢀ
formed on a precoated Sorbfil plates using mixtures of the
following solvents CH2Cl2, CHCl3, and Et2O, the spots were
visualized using solutions of KMnO4 and phosphomolybdic
acid in EtOH. Elemental analyses were performed on an EA
1110 CHNSꢀO elemental analyzer. For column chromatoꢀ
graphy, silica gel (0.06—0.2 mm, Alfa Aesar) and neutral Al2O3
(0.05—0.15 mm, pH 7.0 0.5, SigmaꢀAldrich) were used, the
same solvent mixtures as for TLC were used as eluents.
ester molecule by other bond type, perhaps, by the Hꢀ
bond. In H spectra, the proton of the alcohol hydroxy
1
group resonates in the low field ( 8.5—11.0) suggesting its
strong deshielding by the electronꢀwithdrawing SO2O
group. Adding alcohol to the solution of the adduct results
in the additional signals in the NMR spectrum. Attempts to
remove the alcohol traces by aqueous extraction failed due to
good water solubility of the esters. Upon isolation of esters
14 and 15 by column chromatography on SiO2 or neutral
Al2O3 using diethylamine as an eluent, esters transform
into the corresponding diethylammonium hydrosulfonates.
Dichloroꢀsubstituted derivative 16 with content up to
45% (1H NMR data) is the predominant byꢀproduct of
the ClO2 oxidation of disulfide 1 in organic solvents. Chlorꢀ
ination can be explained by the participation in the reacꢀ
tion of the chloride ions and chlorine radicals, which are
the forms of the exhaustive reduction of the oxidizer.19,20
This reaction direction is favored by both the lack of ClO2
in the reaction mixture (the mixing of the reagents by
method A) and the long reaction time. Adding pyridine to
the reaction mixture leads to a noticeable decrease in the
content of the byꢀproduct 16 in the reaction mixture and
to an increase in the target product yields, since pyridine
binds free H+ and Cl–. Thus, the yields of esters 14 and 15
in the reactions carried out in the presence of pyridine
increases from 45—50 to 85% (1H NMR data). Oxidation
of compound 1 in aqueous pyridine or aqueous alcohols
results quantitatively in sulfonic acid 10.
The attempts to synthesize ester of isobornanesulfinic acid
by oxidation of 1 with 5ꢀfold excess of Pb(OAc)4 in MeOH
following the published procedure9 failed due apparently
to the steric effects of the isobornyl groups and poor coorꢀ
dination of the bulky oxidizing agent to sulfur atoms.
In summary, in the present work the direction of oxiꢀ
dation of diisobornyl disulfide with MCPBA, Pb(OAc)4,
and ClO2 were studied. Oxidation of disulfide 1 with equivꢀ
alent amount of MCPBA yields unstable thiosulfinates
and the increase in the amount of the oxidizer leads to
desulfurization. Lead tetraacetate does not react with diꢀ
sulfide 1 even at prolonged reflux, while ClO2 oxidation
gives wide range of the products with the selectivity deꢀ
pending on the solvent nature, molar reagent ratio, and
the order of the reagent mixing. For instance, an imporꢀ
tant condition for obtaining the oxygenꢀcontaining derivꢀ
atives (sulfinyl chloride, sulfonic acids and their esters) is
the oxidant excess in the reaction mixture (method B).
Sequential addition of ClO2 (oxidation with the lack of
the oxidizer, method A) in low polar heptane leads to
diisobornyl trisulfide in high yield (78%) and, in some
cases, to desulfurization and chlorination.
Bis((1S,2S,4S)ꢀ1,7,7ꢀtrimethylbicyclo[2.2.1]heptꢀ2ꢀyl) disꢀ
ulfide (1). Synthesis of this compound and its physicochemical
characteristics are described in Refs 21 and 22.
MCPBAꢀmediated oxidation of isobornyl disulfide (1). To
a solution of disulfide 1 (0.5 g) in CH2Cl2 (10 mL), 70—75%
MCPBA (0.370 g, 1.5 mmol, technical grade) was slowly added
portionwise. The mixture was stirred for 10 min until complete
consumption of disulfide (TLC monitoring). Then solvent was
removed in vacuo until the volume of the residue was ~3 mL.
The residue was chromatographed on either silica gel or neutral
Al2O3, in both cases CH2Cl2 was used as an eluent. Silica gel
column chromatography gave only products of thiosulfinate
decomposition, i.e., disulfide 1 and thiocamphor 3. Thiosulꢀ
finates 2 were isolated by Al2O3 column chromatography. Thioꢀ
sulfinates 2 are poorly stable compounds, therefore the spectral
studies of these compounds were carried out immediately after
isolation.
(1S,2S,4S)ꢀ1,7,7ꢀTrimethylbicyclo[2.2.1]heptꢀ2ꢀyl (1S,2S,4S)ꢀ
1,7,7ꢀtrimethylbicyclo[2.2.1]heptaneꢀ2ꢀthiosulfinate (2). Mixture
of diastereomers, de 35%. Yield 93%. MS (ESI, 5 kV), m/z
(Irel (%)): 355 [M + H]+ (34). IR, /cm–1: 1076 (S=O). 1H NMR
(CDCl3), : 0.82—1.09 (m, 36 H, Me(8), Me(8´), Me(9), Me(9´),
Me(10), Me(10´)); 1.09—2.64 (several overlapped signals, 28 H,
H(3), H(3´), H(4), H(4´), H(5), H(5´), H(6), H(6´)); 3.13 (dd,
1 H, H(2´)1, J = 9.1 Hz, J = 5.6 Hz); 3.23 (dd, 1 H, H(2´)2,
J = 9.8 Hz, J = 5.8 Hz); 3.39 (dd, 1 H, H(2)1, J = 9.1 Hz,
J = 5.7 Hz); 3.48 (dd, 1 H, H(2)2, J = 9.3 Hz, J = 6.0 Hz).
Decomposition of thiosulfinate 2 in the presence of BF3•Et2O.
Mixture of thiosulfinates were synthesized as described above,
the solvents were removed, and MeOH (5 mL) BF3•Et2O
(2 drops) were added. The mixture was refluxed for 3—4 h until
complete decomposition of thiosulfinates. The products were
purified by column chromatography.
Experimental
Bis((1S,2S,4S)ꢀ1,7,7ꢀtrimethylbicyclo[2.2.1]heptꢀ2ꢀyl) tetraꢀ
sulfide (6). Colorless liquid. Yield 70%. Found (%): C, 59.58;
H, 8.58; S, 31.84. C20H34S4. Calculated (%): C, 59.65; H, 8.51;
S, 31.84. MS (ESI, 5 kV), m/z (Irel (%)): 402 [M]+ (8), 233
IR spectra were recorded on a Shimadzu IR Prestige 21
Fourier transform spectrometer as neat samples or using KBr

Oxidation of diisobornyl disulfide
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 9, September, 2014
2071
[C10H17SSS]+ (8), 201 [C10H17SS]+ (13), 169 [C10H17S]+ (9),
137 [C10H17]+ (58). IR, /cm–1: 578 (C—S), 617 (C—S), 797,
930, 1454, 2953. 1H NMR (CDCl3), : 0.87 (s, 3 H, Me(8)); 0.94
(s, 3 H, Me(9)); 1.09 (s, 3 H, Me(10)); 1.10—1.37 (m, 2 H,
Hendo(5), Hendo(6)); 1.65—1.87 (m, 3 H, H(4), Hexo(5), Hexo(6));
1.87—2.15 (m, 2 H, Hendo(3), Hexo(3)); 3.35 (dd, 1 H, H(2),
J = 9.1 Hz, J = 6.2 Hz). 13C NMR, : 14.2 (C(10)), 20.0 (C(8)),
20.5 (C(9)), 27.4 (C(5)), 38.4 (C(6)), 40.3 (C(3)), 46.0 (C(4)),
47.3 (C(7)), 50.1 (C(1)), 64.0 (C(2)).
2ꢀMethoxyꢀ1,7,7ꢀtrimethylbicyclo[2.2.1]heptane (7), a mixꢀ
ture of diastereomers. Yield 30%. Spectral characteristics are
identical to those published earlier.23
Oxidation of diisobornyl disulfide 1 with ClO2. A. A mixture of
air and ClO2 (0.40 g, 6.0 mmol) was bubbled during 2—3 h
through a solution of disulfide 1 (0.2 g, 0.6 mmil) in an appropriꢀ
ate solvent (10 mL). Prior to use, ClO2 was dried by passing
through the tubes with concentrated H2SO4 and CaCl2. The
course of the reaction was monitored by TLC. The products
were isolated by column chromatography.
OH). 13C NMR, : 12.8 (C(10)), 20.4 (C(8)), 20.6 (C(9)), 26.7
(C(5)), 33.5 (C(6)), 40.0 (C(3)), 44.7 (C(4)), 48.1 (C(7)), 50.6
(C(1)), 70.2 (C(2)).
Methyl (1S,2S,4S)ꢀ1,7,7ꢀtrimethylbicyclo[2.2.1]heptaneꢀ2ꢀ
sulfinate (11), a mixture of diastereomers, was obtained by methꢀ
od A using MeOH as the solvent. Colorless liquid. Total yield
42%. A mixture of diastereomers in a ratio of A : B = 1 : 1.
Found (%): C, 61.62; H, 9.21; S, 15.01. C11H20SO2. Calculatꢀ
ed (%): C, 61.11; H, 9.26; S, 14.81. MS (ESI, 5 kV), m/z
(Irel (%)): 217 [M + H]+ (75), 201 [M + H – OH]+ (15),
149 [CH2=CHCH(CH3)CH(S(O)OH2)CH3]+ (91), 137
[M – CH3OSO]+ (100). IR, /cm–1: 682, 711 (S–O); 970, 999
(C–O); 1122 (S=O). 1H NMR (CDCl3), , diastereomers A, B:
1.18—1.40 (m, 4 H, Hendo(5), Hendo(6)); 1.59—1.84 (m, 6 H,
H(4), Hendo(5), Hexo(6)); diastereomer A: 0.91 (s, 3 H, Me(8));
0.95 (s, 3 H, Me(9)); 1.13 (s, 3 H, Me(10)); 1.82—1.93 (m, 2 H,
Hendo(3), Hexo(3)); 2.65 (dd, 1 H, H(2), J = 9.31 Hz, J = 5.98 Hz);
3.74 (s, 3 H, OCH3)); diastereomer B: 0.90 (s, 3 H, Me(8)); 0.93
(s, 3 H, Me(9)); 1.02 (s, 3 H, Me(10)); 2.08—2.20 (m, 2 H,
Hendo(3), Hexo(3)); 2.79 (dd, 1 H, H(2), J = 9.86 Hz, J = 5.86 Hz);
3.82 (s, 3 H, OCH3). 13C NMR, , diastereomers A, B: 13.7,
13.2 (C(10)); 19.6, 19.8 (C(8)); 20.0 (C(9)); 27.3, 27.4 (C(5));
31.3, 30.7 (C(3)); 39.2, 38.6 (C(6)); 44.7, 44.9 (C(4)); 47.6, 47.7
(C(7)); 49.3, 49.0 (C(1)); 53.1, 54.7 (OCH3); 75.2, 74.3 (C(2)).
Ethyl (1S,2S,4S)ꢀ1,7,7ꢀtrimethylbicyclo[2.2.1]heptaneꢀ2ꢀ
sulfinate (12), a mixture of diastereomers, was obtained by
method A using EtOH as a solvent. Colorless liquid. Accordꢀ
ing to NMR data, total content of the ester 12 in the reacꢀ
tion mixture was 48%. A mixture of diastereomers in a ratio
of A : B = 36 : 64. Found (%): C, 62.81; H, 9.62; S, 13.81.
C12H22SO2. Calculated (%): C, 62.61; H, 9.57; S, 13.91.
MS (ESI, 5 kV), m/z (Irel (%)): 231 [M + H]+ (100), 149
[CH2=CHCH(CH3)CH(S(O)OH2)CH3]+ (10), 137 [C10H17]+
(47). IR, /cm–1: 921 (S—O), 1111 (S=O). 1H (CDCl3), , diasꢀ
tereomers A, B: 1.55—2.10 (m, 14 H, Hendo(3), Hexo(3), H(4),
Hendo(5), Hexo(5), Hendo(6), Hexo(6)); 0.84—1.17 (m, 18 H,
Me(8, 9, 10)); 1.16—1.54 (m, 6 H, OCH2CH3); 4.01—4.34
(m, 4 H, OCH2CH3); diastereomer A: 2.70 (dd, 1 H, H(2),
J = 9.39 Hz, J = 5.87 Hz); diastereomer B: 2.82 (dd, 1 H, H(2),
J = 9.98 Hz, J = 5.87 Hz). 13C NMR, , diastereomers A, B:
13.7, 13.3 (C(10)); 15.8 (CH2CH3); 19.8, 19.6 (C(8)); 20.5, 20.0
(C(9)); 27.2, 27.3 (C(5)); 31.5, 30.8 (C(3)); 39.2, 38.6 (C(6));
44.7, 44.9 (C(4)); 47.5, 48.0 (C(7)); 50.2, 50.1 (C(1)); 64.0, 64.2
(OCH2CH3); 75.2, 74.2 (C(2)).
Isobutyl (1S,2S,4S)ꢀ1,7,7ꢀtrimethylbicyclo[2.2.1]heptaneꢀ2ꢀ
sulfinate (13), a mixture of diastereomers, was obtained by methꢀ
od A using BuiOH as a solvent. Colorless liquid. According to
NMR data, total content of ester 13 in the reaction mixture is
42%. A mixture of diastereomers in a ratio of A : B = 60 : 40.
Found (%): C, 65.19; H, 10.01; S, 12.69. C14H26SO2. Calculatꢀ
ed (%): C, 65.12; H, 10.08; S, 12.40. MS (ESI, 5 kV), m/z
(Irel (%)): 259 [M + H]+ (100), 137 [C10H17]+ (38). IR, /cm–1: 974,
1000 (C—O); 1115 (S=O). 1H NMR (CDCl3), , diastereomers
A, B: 1.54—2.34 (m, 16 H, CH(CH3)2, Hendo(3), Hexo(3),
H(4), Hendo(5), Hexo(5), Hendo(6), Hexo(6)); 3.96 (d, 4 H,
CH2CH(CH3)2, J = 6.46 Hz); diastereomer A: 0.91 (s, 3 H,
Me(8)); 0.96 (s, 3 H, Me(9)); 1.10 (s, 3 H, Me(10)); 2.87 (dd, 1 H,
H(2), J = 9.39 Hz, J = 5.87 Hz); diastereomer B: 0.90 (s, 3 H,
Me(8)); 0.94 (s, 3 H, Me(9)); 0.99 (s, 3 H, Me(10)); 2.95 (dd, 1 H,
H(2), J = 9.98 Hz, J = 5.87 Hz). 13C NMR, , diastereomers A,
B: 13.7, 13.5 (C(10)); 18.6 (C(CH(CH3)2); 19.5 (C(8)); 19.7
B. To a solution of ClO2 (0.12 g, 1.8 mmol) in an appropriate
solvent (10 mL), disulfide 1 (0.2 g, 0.6 mmol) was added and the
mixture was stirred for 0.5—3 h, then the solvent was removed
in vacuo. The course of the reaction was monitored by TLC. The
products were isolated by column chromatography.
Bis((1S,2S,4S)ꢀ1,7,7ꢀtrimethylbicyclo[2.2.1]heptꢀ2ꢀyl) triꢀ
sulfide (8) was obtained by method A using heptane as a solvent.
White powder. Yield 78%. MS (ESI, 5 kV), m/z (Irel (%)): 371
[M + H]+ (100), 137 [C10H17]+ (51). Found (%): C, 64.62;
H, 9.21; S, 25.90. C20H34S3. Calculated (%): C, 64.86; H, 9.19;
S, 25.95. IR, /cm–1: 736, 781, 1375, 1454, 2922. 1H NMR
(CDCl3), : 0.86 (s, 3 H, Me(8)); 0.93 (s, 3 H, Me(9)); 1.06 (s, 3 H,
Me(10)); 1.19—1.29 (m, 2 H, Hendo(5), Hendo(6)); 1.65—1.79
(m, 3 H, H(4), Hexo(5), Hexo(6)); 1.78—2.04 (m, 2 H, Hendo(3),
Hexo(3)); 3.35 (dd, 1 H, H(2), J = 8.83 Hz, J = 6.27 Hz).
13C NMR, : 14.1 (C(10)), 20.0 (C(8)), 20.5 (C(9)), 27.4 (C(5)),
38.4 (C(6)), 40.3 (C(3)), 46.0 (C(4)), 47.3 (C(7)), 50.0 (C(1)),
63.2 (C(2)).
(1S,2S,4S)ꢀ1,7,7ꢀTrimethylbicyclo[2.2.1]heptaneꢀ2ꢀsulfinyl
chloride (9) was obtained by method B. Reaction time was 0.5 h;
CH2Cl2 and H2O were used as the solvents. According to NMR
data, the content of 9 in the reaction mixture was 70—75%.
A mixture of diastereomers in a ratio of A : B = 75 : 25. IR, /cm–1
:
1145 (S=O). 1H NMR (CDCl3), , diastereomer A: 0.92 (s, 3 H,
Me(8)); 0.96 (s, 3 H, Me(9)); 1.11 (s, 3 H, Me(10)); 1.15—1.37
(m, 2 H, Hendo(5), Hendo(6)); 1.60—2.40 (m, 5 H, Hendo(3),
Hexo(3), H(4), Hexo(5), Hexo(6)); 3.53 dd, 1 H, H(2), J = 9.10 Hz,
J = 6.75 Hz). 13C NMR, : 13.9 (C(10)), 19.8 (C(8)), 20.1 (C(9)),
27.1 (C(5)), 33.0 (C(6)), 39.4 (C(3)), 43.1 (C(1)), 44.6 (C(4)),
47.3 (C(7)), 82.8 (C(2)).
(1S,2S,4S)ꢀ1,7,7ꢀTrimethylbicyclo[2.2.1]heptaneꢀ2ꢀsulfonic
acid (10) was obtained by method B; EtOH, H2O were used as
the solvents. Impurities were removed from the reaction mixture by
extraction with CH2Cl2. Colorless liquid. Yield 91%. Found (%):
C, 44.22; H, 9.01; S, 11.86. C10H18SO3•3H2O. Calculated (%):
C, 44.12; H, 8.82; S, 11.76. MS (ESI, 5 kV), m/z (Irel (%)): 220
[M + 2H]+ (50), 202 [M – H2O]+ (33), 137 [C10H17]+ (92).
IR, /cm–1: 883 (S—O), 1067 (SO2), 1179 (SO2), 3441 (OH).
1H NMR (CDCl3), : 0.92 (s, 3 H, Me(8)); 1.10 (s, 3 H, Me(9));
1.23 (s, 3 H, Me(10)); 1.16—1.38 (m, 2 H, Hendo(5), Hendo(6));
1.58—1.92 (m, 3 H, H(4), Hexo(5), Hexo(6)); 2.17—2.39 (m, 2 H,
Hendo(3), Hexo(3)); 3.32 (t, 1 H, H(2), J = 8.82 Hz); 9.42 (s, 1 H,

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Izmest´ev et al.
(C(9)); 27.1, 27.2 (C(5)); 28.0, 29.0 (CH(CH3)2)); 32.5, 31.0
(C(3)); 38.9, 38.5 (C(6)); 44.8, 44.6 (C(4)); 47.7, 47.8 (C(7));
49.5, 49.3 (C(1)); 74.6, 74.0 (C(2)); 75.6, 76.5 (CH2CH(CH3)2).
Ethyl (1S,2S,4S)ꢀ1,7,7ꢀtrimethylbicyclo[2.2.1]heptaneꢀ2ꢀ
sulfonate (14) was obtained by method A using ClO2 (0.48 g,
7.2 mmol) as an oxidant and pyridine and EtOH as the solꢀ
vents. Colorless liquid. Yield 85%. Found (%): C, 57.19;
H, 9.69; S, 10.69. C12H22SO3•C2H5OH. Calculated (%): C,
57.53; H, 9.59; S, 10.96. MS (ESI, 5 kV), m/z (Irel (%)):
, diastereomer A, B: 13.4, 14.1 (C(10)); 14.6 (CH2CH3); 19.9,
20.0 (C(8)); 20.0 (C(9)); 27.5, 27.3 (C(5)); 31.7, 33.7 (C(3));
39.2, 39.1 (C(6)); 41.5 (CH2CH3)); 45.1, 44.9 (C(4)); 47.8, 47.6
(C(7)); 49.3, 48.7 (C(1)); 68.7, 73.1 (C(2)).
(1S,2S,4S)ꢀ2ꢀDiethylaminosulfanylꢀ1,7,7ꢀtrimethylbicycloꢀ
[2.2.1]heptane (19). A roundꢀbottom flask cooled to –25 C was
charged with Et2NH (15—20 mL) followed by addition of NCS
(0.133 g, 1.0 mmol). The mixture was stirred for 5 min, then
isobornyl thiol 18 (0.170 g, 1 mmol) in anhydrous THF (3 mL)
was added and stirring was continued for 15 min. After warming
up to 20 C, the solvent and amine excess were removed in vacuo
and the residue was purified by column chromatography (elution
248 [M
+
2H]+ (37), 217 [C10H17SO3]+ (71), 149
[CH2=CHCH(CH3)CH(S(O)OH2)CH3]+ (61), 137 [C10H17]+
(60). IR, /cm–1: 925 (S—O); 1010 (sym(SO2).); 1055, 1172
(asym(SO2).); 1228. 1H NMR (CDCl3), : 0.90 (s 3 H, Me(8));
1.08 (s, 3 H, Me(9)); 1.20 (s, 3 H, Me(10)); 1.13—1.35 (m, 2 H,
Hendo(5), Hendo(6)); 1.35 (t, 6 H, CH2CH3, J = 7.04 Hz);
1.54—2.00 (m, 4 H, Hendo(3), H(4), Hexo(5), Hexo(6)); 2.16—2.34
(m, 1 H, Hexo(3)); 3.26 (t, 1 H, H(2), J = 8.80 Hz); 4.14—4.32
(m, 2 H, CH2CH3). 13C NMR, : 12.7 (C(10)), 14.7 (CH2CH3),
20.4 (C(8)), 20.6 (C(9)), 26.7 (C(5)), 33.5 (C(6)), 40.0 (C(3)),
44.7 (C(4)), 48.0 (C(7)), 50.4 (C(1)), 67.1 (CH2CH3),
69.9 (C(2)).
with ethyl acetate). Colorless liquid. Yield 90%. []22 + 40.5
D
(c 0.31, Me2CO). Found (%): C, 69.62; H, 11.30; N, 5.75; S, 13.24.
C14H27NS. Calculated (%): C, 69.65; H, 11.27; N, 5.80; S, 13.28.
IR, /cm–1: 642 (C—S), 898 (S—N). 1H NMR (CDCl3), : 0.78
(s, 3 H, Me(8)); 0.83 (s, 3 H, Me(9)); 1.05 (s, 3 H, Me(10));
1.10—1.18 (m, 1 H, Hendo(5)); 1.18 (t, 6 H, CH2CH3, J = 7.0 Hz);
1.20—1.31 (m, 1 H, Hendo(6)); 1.61—1.79 (m, 3 H, H(4), Hexo(5),
Hexo(6)); 1.86—1.99 (m, 2 H, Hendo(3), Hexo(3)); 2.69 (dd, 1 H,
H(2), J = 8.4 Hz, J = 7.2 Hz); 2.95 (q, 4 H, CH2CH3, J = 7.0 Hz).
13C NMR, : 13.8 (CH2CH3)), 14.6 (C(10)), 19.7 (C(9)), 20.6
(C(8)), 27.6 (C(5)), 38.3 (C(6)), 41.6 (C(3)), 46.0 (C(4)), 46.8
(C(7)), 49.6 (C(1)), 52.1 (CH2CH3), 56.6 (C(2)).
Isobutyl (1S,2S,4S)ꢀ1,7,7ꢀtrimethylbicyclo[2.2.1]heptaneꢀ2ꢀ
sulfonate (15) was obtained by method A using ClO2 (0.48 g,
7.2 mmol) as an oxidant and BuiOH as a solvent. Colorless
liquid. Yield 78%. Found (%): C, 61.59; H, 10.39; S, 9.49.
C14H26SO3•C4H9OH. Calculated (%): C, 62.07; H, 10.34;
S, 9.20. MS (ESI, 5 kV), m/z (Irel (%)): 276 [M + 2H]+ (43),
217 [C10H17SO3]+ (59), 149 [CH2=CHCH(CH3)CH(S(O)ꢀ
OH2)CH3]+ (68), 137 [C10H17]+ (65). IR, /cm–1: 927 (S—O);
1013 (sym(SO2).); 1056, 1178 (asym(SO2).); 1225. 1H NMR
(CDCl3), : 0.90 (s, 3 H, Me(8)); 0.98 (t, 6 H, CH2CH(CH3)2,
J = 6.75 Hz); 1.09 (s, 3 H, Me(9)); 1.22 (s, 3 H, Me(10));
1.16—1.32 (m, 2 H, Hendo(5), Hendo(6)); 1.59—1.87 (m, 4 H,
Hendo(3), H(4), Hexo(5), Hexo(6)); 1.84—1.95 (m, 1 H, CH(CH3)2);
2.27 (td, 1 H, Hexo(3), J = 8.51 Hz, J = 4.11 Hz); 3.28 (t, 1 H,
H(2), J = 8.80 Hz); 3.96 (d, 2 H, CH2CH(CH3)2, J = 6.46 Hz).
13C NMR, : 12.8 (C(10)), 18.7 (CH(CH3)2), 20.4 (C(8)),
20.6 (C(9)), 26.7 (C(5)), 29.0 (CH(CH3)2), 35.5 (C(3)), 40.0
(C(6)), 44.7 (C(4)), 48.0 (C(7)), 50.4 (C(1)), 69.9 (C(2)), 76.7
(CH2CH(CH3)2).
The authors are very grateful to E. N. Zainullina, S. P.
Kuznetsov, I. N. Alekseev, and E. U. Ipatova of the Laboꢀ
ratory of the Institute of Chemistry of the Komi Sientific
Center of Ural Branch of RAS for the spectral meaꢀ
surements.
This work was financially supported by the Russian
Foundation for Basic Research and the Government of
the Komi Republic (Project No. 13ꢀ03ꢀ98807_p_sever)
and Ural Division of the Russian Academy of Sciences
(Program No. 1 for the Development of Chemistry and
Materials Science of RAS, Project No. 12ꢀTꢀ3ꢀ1030).
References
(1S,2S,4S)ꢀ2ꢀChloroꢀ1ꢀchloromethylꢀ7,7ꢀdimethylbicycloꢀ
[2.2.1]heptane (16) was obtained by method A. Reaction time
was 2.5 h. Yield up to 45%. Spectral data of the sample are in
agreement with those published earlier.24
1. W. Oppolzer, R. Moretti, Ch. Zhou, Helv. Chim. Acta, 1994,
77, 2363.
2. I. Fernadez, N. Khiar, J. M. Llera, F. Alcudia, J. Org. Chem.,
1992, 57, 6789.
3. D. A. Cogan, G. Liu, K. Kim, B. J. Backes, J. A. Ellman,
J. Am. Chem. Soc., 1998, 120, 8011.
4. I. Fernandez, N. Khiar, Chem. Rev., 2003, 103, 3651.
5. RF Pat. 2119332; Byull. Izobret. [Invention Bull.], 1998,
No. 27 (in Russian).
6. F. Freeman, Ch. N. Angeletakis, J. Am. Chem. Soc., 1982,
104, 5766.
7. F. Freeman, Ch. N. Angeletakis, T. Maricich, J. Am. Chem.
Soc., 1981, 103, 6232.
8. F. Freeman, Ch. Lee, J. Org. Chem., 1988, 53, 1263.
9. L. Field, Ch. B. Hoelzel, J. M. Locke, J. Am. Chem. Soc.,
1962, 84, 847.
10. RF Pat. 2289574; Byull. Isobret. [Invention Bull.], 2006,
No. 35 (in Russian).
(1S,2S,4S)ꢀN,NꢀDiethylꢀ1,7,7ꢀtrimethylbicyclo[2.2.1]heptꢀ
aneꢀ2ꢀsulfinamide (17). The reaction mixture containing comꢀ
pound 9 was mixed with Et2NH following the known proceꢀ
dure.25 Colorless heavy liquid. Total yield 53%. A mixture of
diastereomers in a ratio of A : B = 63 : 37. Found (%): C, 65.37;
H, 10.53; S, 12.40; N, 5.48. C14H27NOS. Calculated (%):
C, 65.32; H, 10.57; S, 12.45; N, 5.44. MS (ESI, 5 kV), m/z
(Irel (%)): 258 [M + H]+ (100), 240 [M + H – OH]+ (22), 137
[C10H17]+ (40). IR, /cm–1: 1061 (S=O), 893 (S–N). 1H NMR
(CDCl3), , diastereomers A, B: 1.08—1.46 (m, 16 H, CH2CH3,
Hendo(5), Hendo(6)); 1.45—1.84 (m, 8 H, Hendo(3), H(4), Hexo(5),
Hexo(6)); 2.93—3.35 (m, 8 H, CH2CH3); diastereomer A: 0.86
(s, 3 H, Me(8)); 0.98 (s, 3 H, Me(9)); 1.21 (s, 3 H, Me(10));
2.12—2.24 (m, 1 H, Hexo(3)); 2.82 (dd, 1 H, H(2), J = 9.98 Hz,
J = 5.87 Hz); diastereomer B: 0.88 (s, 3 H, Me(8)); 0.94 (s, 3 H,
Me(9)); 1.19 (s, 3 H, Me(10)); 1.75—1.84 (m, 1 H, Hexo(3));
2.63 (dd, 1 H, H(2), J = 9.83 Hz, J = 5.72 Hz). 13C NMR,
11. RF Pat. 2302407; Byull. Isobret. [Invention Bull.], 2007,
No. 19 (in Russian).

Oxidation of diisobornyl disulfide
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 9, September, 2014
2073
12. O. M. Lezina, S. A. Pubtsova, A. V. Kuchin, Russ. J. Org.
Chem. (Engl. Transl.), 2011, 47, 1249 [Zh. Org. Khim., 2011,
47, 1230].
20. I. I. Nikitin, Khimiya kislorodnykh soedinenii galogenov
[Chemistry of Oxygen Compounds of Halogens], Nauka, Mosꢀ
cow, 1986, 104 pp. (in Russian).
13. E. S. Izmest´ev, D. V. Sudarikov, S. A. Rubtsova, A. V.
Kuchin, Chem. Nat. Compd. (Engl. Transl.), 2011, 47, 46
[Khim. Prir. Soedin., 2011, No. 1, 43].
14. P. Rose, M. Whiteman, Ph. K. Moore, Y. Zh. Zhu, Nat. Prod.
Rep., 2005, 22, 351.
21. A. W. Snow, E. E. Foos, Synthesis, 2003, 509.
22. E. S. Izmest´ev, D. V. Sudarikov, S. A. Rubtsova, P. A.
Slepukhin, A. V. Kuchin, Russ. J. Org. Chem. (Engl. Transl.),
2012, 48, 184 [Zh. Org. Khim., 2012, 48, 197].
23. K. Zhang, J. Am. Chem. Soc., 2011, 133, 3242.
24. H. Parlar, S. Gaeb, A. Michna, F. Korte, Chemosphere, 1976,
5, 217.
15. V. Gupta, K. S. Carroll, Biochim. Biophys. Acta, Gen. Subj.,
2014, 1840, 847.
16. P. Brownbridge, I. C. Jowett, Synthesis, 1988, 252.
17. O. M. Lezina, S. A. Rubtsova, D. V. Belykh, P. A. Slepukhin,
A. V. Kutchin, Russ. J. Org. Chem. (Engl. Transl.), 2013, 49,
112 [Zh. Org. Khim., 2013, 49, 117].
25. HobenꢀWeyl, Methoden der Organischen Chemie, Georg Thiꢀ
eme Verlag, Stuttgart, 1963, 1006 pp.
18. K. L. Handoo, S. K. Handoo, K. Gadru, A. Kaul, Tetraꢀ
hedron Lett., 1985, 26, 1765.
19. M. Z. Yakupov, N. M. Shishlov, V. V. Shereshovets, U. B.
Imashev, Petrol. Chem. (Engl. Transl.), 2001, 41, 48 [Nefteꢀ
chimiya, 2001, 41, 52].
Received January 29, 2014;
in revised form April 4, 2014