Asymmetric oxidation of hetaryl neomenthyl sulfides

Article abstract of DOI:10.1134/S1070428012010186

Previously unknown diastereoisomeric sulfoxides were synthesized by asymmetric oxidation of 2-neomenthylsulfanyl-substituted 1H-imidazole, 1-methyl-1H-imidazole, and 1H-benzimidazole. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070428012010186

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 1, pp. 113–118. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © M.Ya. Demakova, D.V. Sudarikov, S.A. Rubtsova, P.A. Slepukhin, A.V. Kutchin, 2012, published in Zhurnal Organicheskoi Khimii,
2012, Vol. 48, No. 1, pp. 118–123.
Asymmetric Oxidation of Hetaryl Neomenthyl Sulfides
M. Ya. Demakovaa, D. V. Sudarikova, S. A. Rubtsovaa, P. A. Slepukhinb, and A. V. Kutchina
a Institute of Chemistry, Komi Research Center, Ural Division, Russian Academy of Sciences,
Pervomaiskaya 48, Syktyvkar, 167982 Russia
e-mail: sudarikov-dv@chemi.komisc.ru
b Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences,
ul. S. Kovalevskoi 20, Yekaterinburg, 620219 Russia
Received April 7, 2011
Abstract—Previously unknown diastereoisomeric sulfoxides were synthesized by asymmetric oxidation of
2-neomenthylsulfanyl-substituted 1H-imidazole, 1-methyl-1H-imidazole, and 1H-benzimidazole.
DOI: 10.1134/S1070428012010186
Many chiral sulfoxides containing a heterocyclic
fragment exhibit interesting biological properties and
are promising as therapeutic agents. For example,
omeprazole (benzimidazole-containing sulfoxide) and
some its derivatives are used for the treatment of ulcers
[1]. Imidazole-containing drug OPC-29030 is used as
platelet adhesion inhibitor [2]. Some medicines of this
series act as anti-inflammatory and analgesic drugs [3].
Menthol and its derivatives are components of
over-the-counter pharmaceutical preparations for the
treatment of chill and rheumatism, muscle pain relax-
ants, and anti-rhinitis, soporific, and cardiac prepara-
tions [4]. Menthol is used as chiral auxiliary in organic
asymmetric syntheses [5]. Thus introduction of a chiral
menthane fragment into molecules containing an imid-
azole fragment is expected, on the one hand, to give
rise to new pharmacological properties and, on the
other, to ensure subsequent asymmetric transforma-
tions with optically active substances.
In the present work we were the first to synthesize
imidazole- and benzimidazole-containing neomenthyl
sulfoxides (Scheme 1). The corresponding initial neo-
menthyl sulfides, 2-neomenthylsulfanyl-1H-imidazole
(Ia), 1-methyl-2-neomenthylsulfanyl-1H-imidazole
(Ib), and 2-neomenthylsulfanyl-1H-benzimidazole
(Ic), were synthesized previously by reaction of
L-menthyl p-toluenesulfonate with heterocyclic thiols
[6]. Sulfides Ia–Ic were subjected to oxidation with
achiral oxidants, m-chloroperoxybenzoic acid
(m-CPBA), tert-butyl hydroperoxide (TBHP)–vanadyl
acetylacetonate [VO(acac)2], and cumene hydroper-
oxide (CHP)–VO(acac)2, as well as with chiral Bolm
and Sharpless systems. As a result, the following stereo-
isomeric sulfoxides were obtained: 2-{(R)-[(1S,2S,5R)-
2-isopropyl-5-methylcyclohexyl]sulfinyl}-1H-imida-
zole (IIa), 2-{(S)-[(1S,2S,5R)-2-isopropyl-5-methylcy-
clohexyl]sulfinyl}-1H-imidazole (IIIa), 1-methyl-2-
{(RS)-[(1S,2S,5R)-2-isopropyl-5-methylcyclohexyl]-
sulfinyl}-1H-imidazole (IIb/IIIb), 2-{(R)-[(1S,2S,5R)-
2-isopropyl-5-methylcyclohexyl)sulfinyl]-1H-benz-
imidazole (IIc), and 2-{(S)-[(1S,2S,5R)-2-isopropyl-5-
methylcyclohexyl]sulfinyl}-1H-benzimidazole (IIIc)
(Table 1).
Scheme 1.
Me
Me
7 Me
5
[O]
+
3
1
R
R
R
S
S
S
Modified Sharpless oxidation ensured the highest
enantiomeric excess. In the Sharpless oxidation of
sulfide Ia diastereoisomer IIa was formed as the major
product; by contrast, sulfoxide IIIa predominated in
the reactions with other oxidants. Likewise, Bolm
oxidation of sulfide Ic afforded mainly diastereoisomer
IIc, whereas sulfoxide IIIc was formed mainly when
other oxidants were used. In all the examined cases the
O–
O–
9
Me
10
Me
Me
Me
Ia–Ic
Me
Me
IIa–IIc
IIIa–IIIc
(c).
6′Me
N
N
N
R =
(a),
(b),
N
N
H
H
N
113

DEMAKOVA et al.
114
Table 1. Asymmetric oxidation of neomenthylsulfanylimidazoles Ia–Ic
Initial sulfide no.
Oxidant
m-CPBA
Ratio II:III
Yield, %
de
34:66
25:75
44:56
16:84
95:50
32:68
42:58
45:55
36:64
21:79
46:54
40:60
34:66
32:68
78:22
75
83
84
85
72
76
81
67
73
69
56
59
61
41
62
32
50
12
68
90
36
16
10
28
58
08
20
32
36
56
Ia
Ia
Ia
Ia
Ia
Ib
Ib
Ib
Ib
Ib
Ic
Ic
Ic
Ic
Ic
TBHP/VO(acac)2
CHP/VO(acac)2
Bolma
Sharplessb
m-CPBA
TBHP/VO(acac)2
CHP/VO(acac)2
Bolma
Sharplessb
m-CPBA
TBHP/VO(acac)2
CHP/VO(acac)2
Bolma
Sharplessb
a
Ratio sulfide I–VO(acac)2–L–H2O2 50:1:1.5:50; L stands for (S,S)-(+)-N,N′-bis(3,5-di-tert-butylsalicylidene)cyclohexane-1,2-diamine.
Ratio sulfide–(+)-DET–TBHP–Ti(i-PrO)4–H2O–EtN(Pr-i)2 1:2:1:1:1:1; DET is diethyl tartrate.
b
oxidation of sulfide Ib gave diastereoisomer IIIb as
the major product.
molecular proton transfer, as shown previously for
solutions of imidazole- and benzimidazole-containing
compounds. Analysis of the Raman spectra confirmed
the existence of charged imidazolium ions in which
variation of charge on the methine carbon atoms leads
to degeneration of the corresponding 13C signals in the
NMR spectra [7] (Scheme 2). Unlike sulfides Ia and
Ic, the 13C NMR spectra of sulfoxides IIa, IIc, IIIa,
and IIIc contained signals from all CH carbon atoms
in the heterocyclic fragment, for the NH proton was
fixed as a result of formation of intramolecular hydro-
gen bond with the sulfoxide oxygen atom.
Thus in most cases the major stereoisomer is that in
which the sulfoxide oxygen atom is oriented toward
the isopropyl group, while the oxidation with chiral
catalytic systems in some cases favors formation of
diastereoisomer in which the sulfoxide oxygen atom is
oriented to the opposite side. The latter configuration
is more favorable from the viewpoint of stereochem-
istry, for equatorial isopropyl group should create
stronger steric hindrances toward the neighboring axial
sulfanyl group. Molecules of imidazolyl and benz-
imidazolyl sulfides in solution form associates through
N–H···N hydrogen bonds. Presumably, such arrange-
ment of molecules in chain associates facilitates
oxidant approach to the sulfide bond at the side cor-
responding to the isopropyl group.
The structure and absolute configurations of com-
pounds IIa, IIc, and IIIa were determined by X-ray
analysis. The configuration of sulfoxide IIIc was
determined by comparing with diastereoisomeric sulf-
All diastereoisomeric sulfoxides were isolated by
column chromatography on silica gel. Their IR spectra
contained absorption bands in the region 1010–
1050 cm–1, which are typical of sulfoxide group. Com-
Scheme 2.
H
H
H+
N
N
N
N
1
pounds II and III displayed in the H and 13C NMR
N
N
spectra signals assignable to both neomenthyl and
heterocyclic fragments. The 13C NMR spectra of initial
sulfides Ia and Ic in nonpolar solvents lacked signals
from CH carbon atoms because of intra- and inter-
H
H
–H+
–H+
N
N
N
N
H
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 1 2012

ASYMMETRIC OXIDATION OF HETARYL NEOMENTHYL SULFIDES
C13
115
C13
C7
C7
N1
C8
C9
C2
C3
S1
C1
O1
C8
C9
C6
C5
C4
C6
O1
N1
C11
C5
N2
C4
C10
S1
C10
C11
C1
N2
C2
C12
C3
C12
Fig. 1. Structure of the molecule of 2-{(R)-[(1S,2S,5R)-2-
isopropyl-5-methylcyclohexyl]sulfinyl}-1H-imidazole (IIa)
according to the X-ray diffraction data.
Fig. 2. Structure of the molecule of 2-{(S)-[(1S,2S,5R)-2-
isopropyl-5-methylcyclohexyl]sulfinyl}-1H-imidazole (IIIa)
according to the X-ray diffraction data.
oxide IIc. We failed to assign absolute configuration of
the sulfur atom in sulfoxides IIb and IIIb.
sulfides using chiral catalytic systems. The configura-
tion of the major diastereoisomer of 1H-imidazole- and
benzimidazole-containing sulfoxides is determined by
the oxidizing system and substrate nature.
According to the X-ray diffraction data, isomeric
sulfoxides IIa and IIIa (Figs. 1, 2) crystallized in the
chiral space group belonging to orthorhombic crystal
system. Like sulfide Ia, the crystal packing of IIa and
IIIa is formed by chains of molecules linked through
intermolecular hydrogen bonds N–H···N along the
a axis (Table 2). The sulfoxide oxygen atom in both
stereoisomeric sulfoxides lies in the heteroring plane
and is oriented toward the N–H bond (the torsion angle
N2C2S1O1 is 12.7° in molecule IIa and –17.1° in IIIa).
EXPERIMENTAL
The IR spectra were recorded on a Shimadzu IR
Prestige 21 spectrometer with Fourier transform from
samples prepared as thin films or KBr pellets. The
melting points were determined on a Sanyo Gallen-
1
kamp melting point apparatus. The H and 13C NMR
spectra were recorded on a Bruker Avance-300 spec-
trometer at 300.17 and 75.48 MHz, respectively, using
Unlike compounds IIa and IIIa, sulfoxide IIc
(Fig. 3) crystallized in the base-centered space group
(monoclinic crystal system). The crystal packing of IIc
consists of stacks formed by non-centrosymmetric
dimers that are linked through intermolecular hydrogen
bonds N–H···O–S (Table 2). The sulfoxide oxygen
atom is oriented toward the N–H bond in the azole ring
plane (torsion angle N1C2S1O2 –12.3°). Presumably,
molecular chains like those observed for sulfoxides IIa
and IIIa cannot be formed because of unfavorable
contact between the sulfinyl group and bulky benz-
imidazole fragment. Crystal packings of chiral azolyl
sulfoxides are characterized by competition of inter-
molecular hydrogen bonds formed between different
polar groups, and prevalence of one or another interac-
tion is determined by steric factors.
1
CDCl3 as solvent and reference. The H and 13C
signals were assigned with the aid of two-dimensional
C15
C16
C14
C3
N2
C2
C13
C12
C8
C4
C5
S1
C1
C11
C9
C10
N1
O2
C7
C6
C17
Thus chiral neomenthyl imidazolyl sulfoxides can
be synthesized in high yield and with high diastereo-
isomeric excess (de) by oxidation of the corresponding
Fig. 3. Structure of the molecule of 2-{(R)-[(1S,2S,5R)-2-
isopropyl-5-methylcyclohexyl]sulfinyl}-1H-benzimidazole
(IIc) according to the X-ray diffraction data.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 1 2012

DEMAKOVA et al.
116
Table 2. Hydrogen bonds D–H···A in the crystalline structures of compounds IIa, IIc, and IIIa according to the X-ray
diffraction data
Compound no.
D–H, Å
H···A, Å
∠DHA, deg
D···A, Å
A
IIa
IIIa
IIc
N2–H2 0.831(15)
N2–H2 0.79(2)
N1–H1 0.95(2)
2.080(15)
2.206(2)0
1.90(2)00
167(1)
173(2)
2.895(3)
2.988(3)
2.799(3)
N1 [x + 1/2, –y + 3/2, –z + 1]
N1 [x + 1/2, –y + 3/2, –z]
O2 [–x + 1, y, –z + 2]
00.156.3(12)
1
homo- (1H–1H COSY, H–1H NOESY) and hetero-
chloroform under vigorous stirring at 0°C. The mixture
was continuously stirred for 5 h, and dry gaseous
ammonia was bubbled through it. The curdy material
(ammonium salt) was filtered off, the solvent was
distilled off under reduced pressure, and the residue
was separated by column chromatography on silica gel
using chloroform–diethyl ether (50:1) as eluent.
nuclear correlation techniques (1H–13C HSQC, H–13C
HMBC). The diastereoisomeric excess (de) values
were calculated from the H NMR data, by the inten-
1
1
sity ratio of signals from the CH proton neighboring to
the sulfoxide group. The optical rotations were meas-
ured on a Krüss P3002RS automatic digital polarim-
eter. Thin-layer chromatography was performed on
Sorbfil plates using heptane–diethyl ether as eluent;
spots were developed by treatment with a solution of
phosphomolybdic acid in ethanol or with a solution of
KMnO4. The elemental compositions were determined
on an EA 1110 CHNS-O automatic analyzer. All reac-
tions were carried out using freshly distilled solvents.
Commercially available reagents were not subjected to
additional purification. Silica gel (0.06–0.2 mm; Alfa
Aesar) was used for column chromatography (eluent
chloroform–diethyl ether).
Oxidation of sulfides Ia–Ic with TBHP (CHP)–
VO(acac)2 (general procedure). A flask equipped with
a stirrer and a dropping funnel was charged with
1 mmol of sulfide Ia–Ic and 0.01 mmol of VO(acac)2
dissolved in 5 ml of chloroform. A solution of 1 mmol
of tert-butyl or cumene hydroperoxide in chloroform
was added under stirring, the mixture was stirred for
1 h at room temperature, an aqueous solution of FeSO4
and citric acid was added, and the mixture was ex-
tracted with diethyl ether (3×15 ml). The extract was
washed with saturated aqueous solutions of NaHCO3
and NaCl and dried over Na2SO4, the solvent was
distilled off, and the residue was subjected to column
chromatography on silica gel using chloroform–diethyl
ether (50:1) as eluent.
X-Ray analysis was performed on an Xcalibur 3
automatic four-circle diffractometer [CCD detector,
λMoKα 0.71073 Å, temperature 295(2) K]. Standard
procedures [8] were applied to data acquisition and
processing; no correction for absorption was intro-
duced. The structures were solved and refined (by
least-squares procedure with respect to F2 in full-
matrix anisotropic approximation for non-hydrogen
atoms ) using SHELX software package [9]. Hydrogen
atoms attached to carbons were placed into positions
calculated on the basis of geometry considerations and
were refined in isotropic approximation with depend-
ent thermal parameters using the riding model; the
positions of NH protons were determined by the direct
method and were refined independently. The results of
X-ray diffraction experiments were deposited to the
Cambridge Crystallographic Data Centre (entry
nos. CCDC 818 569–818571) and are available at
www.ccdc.cam.ac.uk/data_request/cif.
Asymmetric oxidation with modified Sharpless
system (general procedure). Titanium(IV) isopropox-
ide, 0.84 g (3 mmol), was quickly added to a solution
of 1.24 g (6 mmol) of (R,R)-DET in 10 ml of methyl-
ene chloride maintained at 16°C. After 2.5 min, 54 μl
of water was slowly added drop by drop in 15-s
intervals under vigorous stirring. The mixture was
stirred for 20 min at 16°C and cooled to 0°C, 3 mmol
of sulfide Ia–Ic and 6 mmol of cumene hydroperoxide
were quickly added, the mixture was stirred for 16 h,
a solution of 3 g (10.8 mmol) of FeSO4 and 1 g
(4.8 mmol) of citric acid in 30 ml of water, 15 ml of
dioxane, and 25 ml of methylene chloride were added,
the mixture was stirred for 15 min, the organic phase
was separated, and the aqueous phase was extracted
with methylene chloride (3×20 ml). The extracts were
combined with the organic phase and treated with
50 ml of 2 M aqueous sodium hydroxide for 1 h under
vigorous stirring. The aqueous phase was extracted
with methylene chloride (3×20 ml), and the extracts
Oxidation of sulfides Ia–Ic with m-chloroperoxy-
benzoic acid (general procedure). A solution of
0.246 g (1 mmol) of 70% m-chloroperoxybenzoic acid
in 25 ml of chloroform was slowly added dropwise to
a solution of 1 mmol of sulfide Ia–Ic in 5 ml of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 1 2012

ASYMMETRIC OXIDATION OF HETARYL NEOMENTHYL SULFIDES
117
were combined with the organic phase, washed with
a saturated aqueous solution of sodium chloride
(25 ml), dried over MgSO4, filtered, and evaporated
under reduced pressure. The residue was separated by
column chromatography on silica gel using chloro-
form–diethyl ether (50:1) as eluent.
tions); S = 1.005 (by F2); van Vleck parameter
0.04 (6); Δρmin/max = 0.185/–0.163 ē/Å3.
2-{(S)-[(1S,2S,5R)-2-Isopropyl-5-methylcyclo-
hexyl]sulfinyl}-1H-imidazole (IIIa). Colorless trans-
parent crystals, mp 129.8°C, [α]D22 = +56.08° (c = 0.51,
1
EtOH). IR spectrum: ν 1008.77 cm–1 (S=O). H NMR
spectrum, δ, ppm: 0.71 d (3H, 7-H, J = 6.5 Hz), 0.89–
1.05 m (1H, 4-Hax), 1.01 d (3H, 10-H, J = 6.4 Hz),
1.07 d (3H, 9-H, J = 6.4 Hz), 1.06–1.23 m (1H, 6-Hax),
1.36–1.52 m (1H, 6-Heq), 1.40–1.55 m (1H, 2-H),
1.53–1.71 m (1H, 5-H), 1.68–1.85 m (1H, 3-Hax),
1.80–1.96 m (1H, 4-Heq), 1.94–2.08 m (1H, 3-Heq),
2.05–2.23 m (1H, 8-H), 3.77–3.86 m (1H, 1-H),
7.19 br.s (1H, 4′-H), 7.21 br.s (1H, 5′-H), 12.35 br.s
(1H, NH). 13C NMR spectrum, δC, ppm: 21.63 (C10),
21.89 (C9), 22.26 (C7), 26.16 (C3), 27.92 (C5), 29.84
(C8), 35.19 (C4), 37.58 (C6), 49.22 (C2), 67.61 (C1),
129.51 (C5′), 130.21 (C4′), 144.13 (C2′). Found, %:
C 61.26; H 8.93; N 11.04; O 6.73; S 12.04.
C13H22N2OS. Calculated, %: C 61.38; H 8.72; N 11.01;
O 6.29; S 12.60.
Asymmetric oxidation using the Bolm catalytic
system (general procedure). Sulfide Ia–Ic, 1 mmol,
was added to a solution of 2.6 mg (0.01 mmol) of
VO(acac)2 and 0.015 mmol of (S,S)-(+)-N,N′-bis(3,5-
di-tert-butylsalicylidene)cyclohexane-1,2-diamine in
2 ml of methylene chloride, the mixture was stirred for
5 min, 1 mmol of 30% hydrogen peroxide was added
dropwise, and the mixture was stirred for 16 h at room
temperature. The reaction was stopped by adding
10 ml of water, the organic phase was separated, and
the aqueous phase was extracted with chloroform
(3 × 15 ml). The extracts were combined with the
organic phase, washed with a solution of Na2CO3
(25 ml) and a saturated aqueous solution of NaCl
(25 ml), dried over MgSO4, filtered, and evaporated
under reduced pressure. The residue was separated by
column chromatography on silica gel using chloro-
form–diethyl ether (50:1) as eluent.
Orthorhombic crystals. Unit cell parameters: a =
10.2973(7), b = 10.3696(6), c = 12.9438(10) Å; α =
β = γ = 90°; V = 1382.12(16) Å3; Z = 4; space group
P212121; dcalc = 1.223 g/cm3; μ = 0.222 mm–1; 2.79 ≤
θ ≤ 30.51°; 9777 reflection intensities were measured,
4005 of which were independent (Rint = 0.0668); R1 =
0.0409 [reflections with I ≥ 2σ(I)], wR2 = 0.0989 (all
reflections); S = 1.007 (by F2); van Vleck parameter
0.10 (7); Δρmin/max = 0.195/–0.287 ē/Å3.
2-{(R)-[(1S,2S,5R)-2-Isopropyl-5-methylcyclo-
hexyl]sulfinyl}-1H-imidazole (IIa). Colorless trans-
parent crystals, mp 129.5°C, [α]D22 = +94.01° (c = 0.80,
1
EtOH). IR spectrum: ν 1043.49 cm–1 (S=O). H NMR
spectrum, δ, ppm: 0.79 d (3H, 7-H, J = 6.5 Hz), 0.89–
1.05 m (1H, 4-Hax), 1.00 d (3H, 10-H, J = 6.5 Hz),
1.06 d (3H, 9-H, J = 6.5 Hz), 1.18–1.34 m (1H, 6-Hax),
1.39–1.56 m (1H, 2-H), 1.58–1.75 m (1H, 3-Hax),
1.83–1.94 m (1H, 4-Heq), 1.93–2.04 m (1H, 6-Heq),
1.89–2.04 m (1H, 3-Heq), 1.95–2.12 m (1H, 8-H),
2.15–2.34 m (1H, 5-H), 3.58–3.65 m (1H, 1-H),
7.25 br.s (1H, 4′-H), 7.28 br.s (1H, 5′-H), 12.33 br.s
(1H, NH). 13C NMR spectrum, δC, ppm: 21.23 (C10),
21.47 (C9), 22.84 (C7), 21.01 (C3), 28.04 (C5), 29.99
(C8), 35.16 (C4), 35.80 (C6), 47.65 (C2), 60.82 (C1),
119.67 (C5′), 131.20 (C4′), 145.93 (C2′). Found, %:
C 61.46; H 8.95; N 11.00; O 6.53; S 12.06.
C13H22N2OS. Calculated, %: C 61.38; H 8.72; N 11.01;
O 6.29; S 12.60.
2-{[(1S,2S,5R)-2-Isopropyl-5-methylcyclohexyl]-
sulfinyl}-1-methyl-1H-imidazole (IIb). Light yellow
liquid, [α]D22 = +48.95° (c = 0.57, EtOH). IR spectrum:
1
ν 1037.70 cm–1 (S=O). H NMR spectrum, δ, ppm:
0.73 d (3H, 9-H, J = 6.5 Hz), 0.88 d (3H, 7-H, J =
6.5 Hz), 0.92 d (3H, 10-H, J = 6.5 Hz), 0.94–1.03 m
(1H, 4-Hax), 1.28–1.39 m (1H, 6-Hax), 1.37–1.48 m
(1H, 2-H), 1.51–1.63 m (1H, 3-Hax), 1.60–1.75 m (1H,
8-H), 1.80–1.94 m (1H, 4-Heq), 1.85–1.95 m (1H,
3-Heq), 2.07–2.26 m (1H, 6-Heq), 3.96 s (3H, NMe),
4.03–1.14 m (1H, 1-H), 6.99 d (1H, 5′-H, J = 0.9 Hz),
7.14 d (1H, 4′-H, J = 0.9 Hz). 13C NMR spectrum, δC,
ppm: 21.15 (C10), 21.27 (C9), 22.74 (C7), 26.45 (C3),
27.99 (C5), 29.63 (C8), 33.92 (NCH3), 35.12 (C4),
35.82 (C6), 47.66 (C2), 60.38 (C1), 124.85 (C5′), 129.30
(C4′), 145.39 (C2′).
Orthorhombic crystals. Unit cell parameters: a =
9.6837(7), b = 11.6447(8), c = 12.8361(14) Å; α = β =
γ = 90°; V = 1447.4(2) Å3; Z = 4; space group P212121;
d
calc = 1.167 g/cm3; μ = 0.212 mm–1; 2.63 ≤ θ ≤ 28.29°;
2-{[(1S,2S,5R)-2-Isopropyl-5-methylcyclohexyl]-
sulfinyl}-1-methyl-1H-imidazole (IIIb). Light yellow
liquid, [α]D22 = –53.28° (c = 0.49, EtOH). IR spectrum:
8652 reflection intensities were measured, 3491 of
which were independent (Rint = 0.0225); R1 = 0.0323
[reflections with I ≥ 2σ(I)], wR2 = 0.0699 (all reflec-
1
ν 1035.77 cm–1 (S=O). H NMR spectrum, δ, ppm:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 1 2012

DEMAKOVA et al.
118
0.73 d (3H, 9-H, J = 6.5 Hz), 0.88 d (3H, 7-H, J =
6.5 Hz), 0.92 d (3H, 10-H, J = 6.5 Hz), 0.94–1.03 m
(1H, 4-Hax), 1.03–1.14 m (1H, 1-H), 1.28–1.39 m (1H,
6-Hax), 1.37–1.48 m (1H, 2-H), 1.51–1.63 m (1H,
3-Hax), 1.60–1.75 m (1H, 8-H), 1.80–1.94 m (1H,
4-Heq), 1.85–1.95 m (1H, 3-Heq), 2.07–2.26 m (1H,
6-Heq), 3.96 s (3H, NMe), 6.99 d (1H, 5′-H, J =
0.9 Hz), 7.14 d (1H, 4′-H, J = 0.9 Hz). 13C NMR spec-
trum, δC, ppm: 22.00 (C10), 22.08 (C9), 22.36 (C7),
25.99 (C3), 27.87 (C5), 29.50 (C8), 33.61 (NCH3),
35.59 (C4), 37.67 (C6), 49.88 (C2), 66.71 (C1), 124.64
(C5′), 129.75 (C4′), 145.39 (C2′). Found, %: C 62.69;
H 8.96; N 11.02; O 6.00; S 11.06. C14H24N2OS. Calcu-
lated, %: C 62.64; H 9.01; N 10.44; O 5.96; S 11.95.
6.6 Hz), 1.05 d (3H, 10-H, J = 6.5 Hz), 1.16–1.32 m
(1H, 6-Hax), 1.49–1.62 m (1H, 2-H), 1.73–1.84 m (1H,
6-Heq), 1.85–1.96 m (1H, 3-Hax), 1.85–1.98 m (1H,
5-H), 1.90–2.01 m (1H, 4-Heq), 2.02–2.12 m (1H,
3-Heq), 2.20–2.33 m (1H, 8-H), 3.92–3.97 m (1H,
1-H), 7.26–7.41 m (2H, 5′-H, 6′-H), 7.56–7.63 m (1H,
7′-H), 7.77–7.84 m (1H, 4′-H), 12.54 br.s (1H, NH).
13C NMR spectrum, δC, ppm: 21.74 (C10), 21.86 (C9),
22.29 (C7), 26.24 (C3), 28.24 (C5), 29.77 (C8), 35.32
(C4), 37.78 (C6), 49.88 (C2), 67.18 (C1), 112.24 (C7′),
120.34 (C4′), 122.96 (C5′), 124.36 (C6′), 134.68 (C3a′),
143.76 (C7a′), 152.22 (C2′). Found, %: C 67.10; H 8.02;
N 9.15; O 5.23; S 10.50. C17H24N2OS. Calculated, %:
C 67.07; H 7.95; N 9.20; O 5.26; S 10.53.
2-{(R)-[(1S,2S,5R)-2-Isopropyl-5-methylcyclo-
hexyl]sulfinyl}-1H-benzimidazole (IIc). Colorless
transparent crystals, mp 145.3°C, [α]D22 = +26.67° (c =
0.54, EtOH). IR spectrum: ν 1039.63 cm–1 (S=O).
1H NMR spectrum, δ, ppm: 0.75 d (3H, 7-H, J =
6.5 Hz), 0.99 q.d (1H, 4-Hax, J = 12.6, 3.5 Hz), 1.18 d
(6H, 9-H, 10-H, J = 6.5 Hz), 1.30 d.d.d (1H, 6-Hax, J =
14.7, 12.7, 5.3 Hz), 1.51–1.61 m (1H, 2-H), 1.73–
1.91 m (1H, 3-Hax), 1.75–1.99 m (1H, 4-Heq), 1.97–
2.11 m (1H, 6-Heq), 2.03–2.16 m (1H, 3-Heq), 2.15–
2.31 m (1H, 8-H), 2.30–2.48 m (1H, 5-H), 3.73–
3.82 m (1H, 1-H), 7.29–7.43 m (2H, 5′-H, 6′-H), 7.59–
7.68 m (1H, 7′-H), 7.81–7.88 m (1H, 4′-H), 12.22 br.s
(1H, NH). 13C NMR spectrum, δC, ppm: 21.46 (C10),
21.53 (C9), 22.80 (C7), 27.28 (C3), 28.22 (C5), 30.44
(C8), 35.14 (C4), 36.28 (C6), 47.62 (C2), 63.14 (C1),
111.93 (C7′), 120.12 (C4′), 122.97 (C5′), 123.86 (C6′),
134.72 (C3a′), 144.74 (C7a′), 151.11 (C2′). Found, %:
C 67.83; H 7.87; N 9.18; O 5.05; S 10.07.
C17H24N2OS. Calculated, %: C 67.07; H 7.95; N 9.20;
O 5.26; S 10.53.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 10-03-00 969) and by the Federal Science and
Innovation Agency (Federal special-purpose program
“Scientific and Scientific–Pedagogical Staff of Innova-
tion Russia,” state contract no. 02.740.11.0081). The
authors thank the staff of Physicochemical Methods
Laboratory (Institute of Chemistry, Komi Research
Center, Ural Division, Russian Academy of Sciences),
namely E.N. Zainullina, S.P. Kuznetsov, and
A.N. Alekseev for recording the NMR spectra and
E.U. Ipatova for recording the IR spectra.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 1 2012