1-oxo-1,3-dithiolanes-synthesis and stereochemistry

Article abstract of DOI:10.1002/mrc.2764

1-Oxo-1,3-dithiolane (4) and its cis- and trans-2-methyl (5,6), -4-methyl (7,8) and -5-methyl (9,10) derivatives were prepared by oxidizing the corresponding 1,3-dithiolanes (1-3) with NaIO₄ in water. The oxides were purified and their isomers separated using thin layer chromatography. The structural characterization was carried out with ¹H and ¹³C NMR spectroscopy and molecular modelling. The sulfoxides 4-6 and 8-10 attain two S(1) type envelopes (sometimes slightly distorted) the S=O _ax envelope greatly dominating. Cis-4-methyl-1-oxo-1,3-dithiolane is a special case exhibiting both two closely related S=O_ax (30 and 27%) as well as S=O_eq (21 and 22%) forms [S(1) and C(4) envelopes, respectively]. The relative energies of these conformations, the values of ¹H-¹H coupling constants and ¹H and ¹³C chemical shifts were estimated by computational methods and they support well the conclusions based on the experimental data. Copyright

Full text of DOI:10.1002/mrc.2764

MRC Letters
Received: 26 January 2011
Revised: 28 March 2011
Accepted: 29 March 2011
Published online in Wiley Online Library: 6 May 2011
(wileyonlinelibrary.com) DOI 10.1002/mrc.2764
1-Oxo-1,3-dithiolanes – synthesis
and stereochemistry
a∗
a,b
c
b
´
´
Kalevi Pihlaja, Jari Sinkkonen, Geza Stajer, Andreas Koch,
and Erich Kleinpeterb
1-Oxo-1,3-dithiolane (4) and its cis- and trans-2-methyl (5,6), -4-methyl (7,8) and -5-methyl (9,10) derivatives were prepared by
oxidizing the corresponding 1,3-dithiolanes (1–3) with NaIO4 in water. The oxides were purified and their isomers separated
using thin layer chromatography. The structural characterization was carried out with 1H and 13C NMR spectroscopy and
molecular modelling. The sulfoxides 4–6 and 8–10 attain two S(1) type envelopes (sometimes slightly distorted) the S Oax
envelope greatly dominating. Cis-4-methyl-1-oxo-1,3-dithiolane is a special case exhibiting both two closely related S Oax
(30 and 27%) as well as S Oeq (21 and 22%) forms [S(1) and C(4) envelopes, respectively]. The relative energies of these
conformations, the values of 1H-1H coupling constants and 1H and 13C chemical shifts were estimated by computational
c
methods and they support well the conclusions based on the experimental data. Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: NMR; 1H NMR; 13C NMR; sulfur heterocycles; conformational analysis; computational chemistry
S3
Introduction
S
S
4
2
2
2
Fewreportsareavailableon1,3-dithiolaneS-oxides. Schanket al.[1]
preparedtheparentcompound(4;Scheme 1). Careyalsoprepared
the parent compound and the oxidized diastereomers formed
from 2-methyl and 2-phenyl-1,3-dithiolanes[2] and found that the
stereoselectivity of oxidation of 1,3-dithiolane (2-R = Me. Ph,
t-Bu) with sodium metaperiodate and m-chloroperbenzoic acid
(MCPBA) gave primarily the trans-1-oxide (for 2-Me trans/cis ratio
was 3 : 2 for the former and 89 : 11 for the latter). However, they did
not carry out detailed analyses of the 1H NMR spectra and hence
left the exact conformations unspecified.
Several reports without detailed structural characterization also
deal with syntheses of some 1,3-dithiolane 1-oxides. Pirkle and
Hamper used 85% MCPBA and 30% H2O2 to prepare 1-oxides from
several 2,2-disubstituted 1,3-dithiolanes to separate their enan-
tiomers by direct HPLC on commercially available chiral stationary
phases.[3] Corich et al.[4] used enantioselective oxidation to ob-
tain enantiomerically pure 1R,2R-1-oxo-2-N, N-dialkylacetamide-
1,3-dithiolanes. A very interesting oxidative approach consists
of oxygen saturation of an 1,3-dithiolane solution in methanol
containing photosensitizer.[5] Schaumann et al.[6] synthesized sev-
eral 2-substituted and 2,2-disubstituted-1-oxo-1,3-dithiolanes by
MCPBA oxidation to utilize them in preparing thioaldehydes and
thioketones. SchulerandSundermeyer[7] inturnappliedthermoly-
sis to obtain thiocarbonyl compounds from 2-CF3-substituted 1,3-
dithiolane oxides, dioxides, trioxides and tetroxides. Few reports
deal with stereoselective S-oxygenation of 2-aryl-1,3-dithiolanes
by rabbit lung enzyme preparations[8], by the flavin-containing
and cytochrome P-450 monooxygenases[9] or stereoselectivity
during fungal sulfoxidations of 1,3-dithiolane and its 2-methyl and
2-t-butyl derivatives.[10]
S
S
S1
3
1
2
O
S1
O
S1
O
S1
2
2
S
S
S
4
5
6
S3
7
S3
8
4
4
2
2
S1
S1
O
O
O
S1
O
S1
2
2
5
5
S3
10
S3
9
Scheme 1. 1,3-Dithiolanes and 1-oxo-1,3-dithiolanes.
corresponding 1,3-dithiolanes[13] (1–3; Scheme 1) and elucidate
their structures with the aid of their NMR spectra and computa-
tional results (Figure 1).
∗
Correspondence to: Kalevi Pihlaja, Department of Chemistry, University of
Turku, Vatselankatu 2, FI-20014, Turku, Finland. E-mail: kpihlaja@utu.fi
a
b
c
Department of Chemistry, University of Turku, Vatselankatu 2, FI-20014, Turku,
Finland
Department of Chemistry, University of Potsdam, Karl-Liebknecht-Str. 24-25,
D-14476 Potsdam (Golm), Germany
Since we studied earlier conformations of 3-oxo-1,3-
oxathiolanes[11] and 3-oxo-1,3-oxathianes,[12] we decided to syn-
thesize several 1-oxo-1,3-dithiolanes (4–10; Scheme 1) from the
Institute of Pharmaceutical Chemistry, University of Szeged, H-6701 Szeged,
Hungary
c
Magn. Reson. Chem. 2011, 49, 443–449
Copyright ꢀ 2011 John Wiley & Sons, Ltd.

K. Pihlaja et al.
Figure 1. The limiting conformations for methyl-1-oxo-1,3-dithiolanes with relative energies in kJ/mol [in square brackets].
Results and Discussion
the S Ogroup, respectively). This is obviously due to the situation
that the axial S O and syn-4-methyl are relatively close to each
other (they are only 2.4 Å apart based on the computations).
In order to assign quantitatively the conformational equilibria
in sulfoxides 4–10, they were studied by computational methods
at the MP2 level of theory (cf. Experimental). The aim was to
elucidatetheconformationswhichcouldbeconcludedtentatively
based on the experimental results. First, the two preferred
conformers (for compound 7 four) and their relative energies (cf.
Figure 1) were computed; in addition, also the NMR parameters
1H (Table 1), 13C chemical shifts (Table 2) and 1H-1H coupling
constants (Table 3) were computed and employed to assign
quantitativelytheconformationalequilibriaofthesulfoxides4–10
The starting 1,3-dithiolanes (1–3) were prepared from
ethanedithiol or 1,2-propanedithiol and aldehydes.[13b] We de-
cided to use sodium metaperiodate as the oxidative agent since
it gives less stereoselectivity than MCPBA,[2] makes it easier to ob-
tain both diastereomers in case of methyl-substituted derivatives.
Accordingly the oxidation of 1–3 with sodium metaperiodate
in water furnished S-oxides (4–10), which were purified and
separated by preparative TLC.
The 1H NMR spectra were analyzed and used to solve
the stereochemistry of 4–10. In comparison with 3-oxo-1,3-
oxathiolanes we studied earlier[4] we can assume that also
1-oxo-1,3-dithiolanes favour a special conformation but in this
case preferably an envelope form with axial S O group. In case of
thelatter,theparentcompound,trans-2-methyl-,cis-4-methyl-and
trans-5-methyl-3-oxo-1,3-oxathiolanesattainedalmostexclusively
(or at least predominantly: 3-oxo-1,3-oxathiolane) the half-chair
typeconformationwithO(1)aboveandC(5)belowtheplane(HC1).
By comparing their vicinal coupling constants with those of 1-oxo-
1,3-dithiolanesinthiswork(Table 3)wecouldtentativelyconclude
that 4–6 and 8–10 must contain one predominant conformation
which was confirmed by the computations (the S Oax envelope
conformers, Fig. 1). Compound 7 instead appears to be almost
equimolar mixture of the S Oax and S Oeq envelope forms as
shown by the values of J4a5s and J4s5a (a and s mean anti and syn to
1
by Boltzmann weighting both chemical shifts and vicinal H-1H
coupling constants of the participating conformers (Tables 1–3).
First we made a conformational search for compounds 4–10.
These calculations corroborated that only S Oax and S Oeq
envelope forms (Fig. 1) need to be considered for compounds
4–6 and 8–10, the S Oax envelope being always the greatly
favored one (91–95.5%). The experimental vicinal 1H-1H coupling
constantsforcompound7(Table 3)alreadyindicatethatitmustbe
an almost equimolar mixture of S Oax and S Oeq envelopes. The
computations gave indeed two almost equally stable S Oax as
well S Oeq envelopes [S(1) and C(4)] for this compound the latter
ones being somewhat distorted in each pair of conformations.
c
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Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2011, 49, 443–449

1-Oxo-1,3-dithiolanes – synthesis and stereochemistry
Table 1. Observed and calculated 1H NMR chemical shifts for 1-oxo-1,3-dithiolane (4) and its cis- and trans-2-methyl (5 and 6, respectively), cis- and
trans-4-methyl (7 and 8, respectively) and cis- and trans-5-methyl derivatives (9 and 10, respectively) in CDCl3
δH/ppm
Compound
H(2s)
H(2a)
H(4s)
H(4a)
H(5s)
H(5a)
%
4 Obsd.
3.89
3.69
3.14
3.64
3.98
3.52
3.86
3.55
3.64
3.66
2.74
3.58
3.41
3.31
2.74
3.26
3.49
3.27
2.61
3.21
2.76
2.04
3.35
2.16
S
Oax
Oeq
91
S
9
Weighted[a]
5 cis
1.67[b]
1.65
4.22
4.36
4.18
4.35
3.43
4.13
3.27
4.08
3.73
3.47
2.92
3.44
3.01
3.46
2.49
3.40
3.31
2.62
3.75
2.69
S
S
Oax
Oeq
94
6
1.54
Weighted[a]
1.64
6 trans
4.23
4.58
3.92
4.53
1.53[b]
1.25
3.69
4.06
3.03
3.99
3.42
3.65
3.02
3.60
3.38
3.39
2.97
3.36
2.94
2.51
3.65
2.59
S
S
Oax
93
7
Oeq
1.68
Weighted[a]
1.28
7 cis
4.02
4.33
3.71
3.63
3.94
3.93
3.98
3.65
5.06
4.16
3.57
4.12
1.62[b]
1.69
1.64
1.36
1.53
1.57
3.79
4.29
4.12
3.68
3.31
3.90
2.96
3.43
3.15
2.61
2.12
2.89
3.42
2.47
2.87
3.75
4.17
3.22
S
S
S
S
Oax(1)
Oax(2)
Oeq(1)
Oeq(2)
30
27
21
22
Weighted[a]
8 trans
4.27
3.98
3.57
3.96
3.83
3.98
4.27
3.99
4.33
4.89
3.78
4.84
1.54[b]
1.55
3.42
3.40
2.95
3.38
2.52
2.16
3.43
2.22
S
S
Oax
Oeq
95
5
1.35
Weighted[a]
1.54
9 cis
4.08
4.00
4.08
4.00
3.87
3.80
3.34
3.77
3.35
3.67
2.92
3.63
3.28
3.30
3.20
3.29
1.54[b]
1.51
3.02
2.97
3.67
3.01
S
Oax
Oeq
94.5
5.5
S
1.42
Weighted[a]
1.50
10 trans
3.91
3.92
3.57
3.91
3.82
3.66
4.18
3.68
3.79
4.09
3.18
4.05
3.10
3.32
2.77
3.30
3.67
3.87
3.00
3.83
1.19[b]
0.95
S
S
Oax
Oeq
95.5
4.5
1.51
Weighted[a]
0.98
[a] Weighted after Boltzmann. [b] Methyl chemical shifts.
The values of the experimental geminal coupling constants J22
,
the experimental NMR parameters, obtained at fast exchange
between the conformers on the NMR time scale. The agreement
is excellent, corroborates the correct position of the computed
conformational equilibria and both chemical shifts and vicinal
1H-1H coupling constants, not only in case of present sulfoxides,
to be useful and precise indications of conformational equilibria
still fast on the NMR time scale.
J44 and J55 do not seem to be dependent on conformations since
the former is always −12.4, the second close to −11.4 and the
latter around −13.3 Hz. The same can be concluded from the
computational results, even if the computed values of the geminal
coupling constants give usually much less negative values than
the experimental ones.
The values of the theoretically calculated 1H-1H coupling
constants (Table 3) were Boltzmann weighted and plotted against
theexperimentalones(Table 3andFig. 2). Rathergoodcorrelation
wasfound(R=0.973,P<0.0001).Goodandverygoodcorrelations
were found also between the experimental and the computed and
Boltzmannweighted1H(Fig. 3;R= 0.960, P < 0.0001)and13CNMR
chemicalshifts(Fig. 4;R=0.994,P<0.0001).Coincidencebetween
experimental and computed NMR parameters proves to be usually
a safe evidence for reliable calculated structures. For this reason,
The 13C NMR spectra were also recorded for compounds 4–10
(Table 2). Carey et al.[2] reported 13C chemical shifts for 4–6 which
were in good agreement with our values; actually, for 5 and 6 they
were systematically 0.4–0.5 ppm smaller than those obtained by
us (Table 2). When comparing 4 to 1,3-dithiolane [δC(2) 34.4 and
δC(4/5) 38.1 ppm][3b] the shift changes caused by the 1-oxo group
are: ꢀδC(2) = 22.4 (21.2), ꢀδC(4) = −7.0 (21.8) and ꢀδC(5) = 16.8
(−2.7) ppm. In parentheses are given the corresponding shift
changes for 1,3-oxathiolane (it should be emphasized that in the
latter it is C(4) which is adjacent to S O group).[4] As to the pairs
of diastereomers, 5 and 6 can be best distinguished by their C(2)
(62.5 vs 67.2 ppm) and CMe (13.4 vs 18.6 ppm), 7 and 8 by their
CMe (22.6 vs 18.1 ppm) and 9 and 10 by their C(2) chemical shifts
1
1H and 13C NMR chemical shifts and the vicinal H-1H coupling
constants in the sulfoxide conformers were applied to control
computed conformational equilibria (Fig. 1). Boltzmann weighted
values have been calculated (Table 3) and were compared with
c
Magn. Reson. Chem. 2011, 49, 443–449
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
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K. Pihlaja et al.
Table 2. Observed and calculated 13C NMR chemical shifts for 1-oxo-1,3-dithiolane (4) and its cis- and trans-2-methyl (5 and6, respectively), cis- and
trans-4-methyl (7 and 8, respectively) and cis- and trans-5-methyl derivatives (9 and 10, respectively) in CDCl3
δC/ppm
Compound
C-2
C-4
C-5
CH3
%
4[2] Obsd.
56.8
56.8
51.5
56.3
31.1
34.0
20.6
32.8
54.9
55.8
53.6
55.6
–
–
–
–
S
Oax
Oeq
91
S
9
Weighted[a]
5 cis
62.5
67.9
60.6
67.5
31.6
36.1
23.4
35.3
56.6
57.5
49.7
57.0
13.35
16.6
12.0
16.3
S
Oax
Oeq
94
6
S
Weighted[a]
6 trans
67.2
73.35
68.4
73.0
31.4
36.2
20.4
35.1
54.2
52.8
55.4
53.0
18.6
21.1
15.8
20.7
S
Oax
93
7
S
Oeq
Weighted[a]
7 cis
55.4
61.6
63.9
57.0
64.7
61.9
43.8
50.1
50.8
33.8
50.55
47.0
64.05
61.3
67.4
64.95
73.8
66.5
22.55
30.0
23.6
23.8
17.15
24.1
S
S
S
S
Oax(1)
Oax(2)
Oeq(1)
Oeq(2)
30
27
21
22
Weighted[a]
8 trans
56.4
59.6
58.0
59.5
44.0
49.6
35.2
48.9
64.05
64.8
64.6
64.8
18.1
18.6
26.45
19.0
S
Oax
Oeq
95
5
S
Weighted[a]
9 cis
54.5
58.2
48.0
57.6
37.1
39.7
28.85
39.1
63.6
65.7
56.2
65.2
11.3
12.1
7.2
S
Oax
Oeq
94.5
5.5
S
Weighted[a]
11.8
10 trans
51.9
37.5
41.2
29.5
40.7
64.3
66.3
66.4
66.3
13.0
9.6
S
Oax
Oeq
55.55
54.75
55.5
95.5
4.5
S
15.9
9.9
Weighted[a]
[a] Weighted after Boltzmann.
(54.5 vs 51.9 ppm). Most of the 13C chemical shifts are not much
different for the diastereomer pairs.
(0.04 mol) 1,2-propanedithiol and 1.4 g (0.044 mol) paraformalde-
hyde and 0.05 g p-toluenesulphonic acid (PTSA) was refluxed in
100 ml CH2Cl2 for 30 min. The solvent was evaporated and the
residue distilled. Colourless oils, 1: bp2kPa 42 ◦C, yield 2.6 g (61%).
Anal. Calcd for C3H6S2 (106.2): C 52.76, H 5.69, S 60.38%. Found C
52.50, H 5.45, S 60.21%. 2: bp0.5 kPa 80 ◦C, yield 3.2 g (66%). Anal.
Calcd for C4H8S2 (120.24): C 3996, H 6.71, S 53.30%. Found C 39.81,
H 6.57, S.53.56%. 3: bp2kPa 42 ◦C, yield 3.4 g (71%).Anal. Calcd for
C4H8S2 (120.237): C 39.96, H 6.71, S 53.30%. Found C 39.67 H 6.54,
S 53.15%.
Conclusion
1-oxo-1,3-dithiolane and its six monomethyl-substituted deriva-
tives were shown to attain envelope forms with either S Oax or
S
Oeq functions. In all, except cis-1-oxo-4-methyl-1,3-dithiolane
(7), the S Oax envelope seems to be greatly favoured (91–95%)
but in 7 the S Oax and cis-4-methyl are relatively close to each
other which makes the S Oeq form almost equally populated.
Preparation of 1-oxo-1,3-dithiolane (4)
1.7 g (16 mmol) 1 in 100 ml MeOH was oxidized with 2.80 g
NaIO4 in 30 ml H2O adding by dropwise under stirring at −5 ◦C.
After stirring in an additional hour, the precipitated NaIO3 was
removed by suction and the filtrate was evaporated to dryness.
The residue was extracted with 100 ml CHCl3, the extract was
washed with water (3 ×10 ml), dried and evaporated leaving 1.5 g
of yellowish oily product. After purification on preparative TLC
plate (Merck 113895, Silica gel 60 F254, 1 mm, developed with
Experimental
Preparation of 1,3-dithiolane (1), 2-methyl-1,3-dithiolane
(2) and 4-methyl-1,3-dithiolane (3)
The mixture of 3.8 g (0.04 mol) ethanedithiol and 1.4 g (0.044 mol)
paraformaldehyde or 1.94 g (0.044 mol) acetaldehyde or 4.33 g
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Magn. Reson. Chem. 2011, 49, 443–449

1-Oxo-1,3-dithiolanes – synthesis and stereochemistry
Table 3. Observed and calculated 1H-1H coupling constants in Hz for 1-oxo-1,3-dithiolanes 4–10 in CDCl3
Compound
J2a2s
J4a4s
J5a5s
J4s5a
J4a5s
J4s5s
J4a5a
J25
%
4 Obsd.
−12.37
−9.95
−7.75
–
−11.38
−8.7
−8.8
–
−13.19
−11.1
−9.75
–
11.64
11.7
0.85
10.7
2.33
1.1
5.02
4.3
6.63
6.35
5.7
1.47
–
S
S
Oax
Oeq
91
11.2
2.0
7.7
–
9
Weighted[a]
4.6
6.3
5 cis
6.7[b]
6.4
−11.54
−8.2
−9.1
–
−13.45
−10.1
−10.1
–
10.55
12.35
3.1
2.83
1.44
5.2
5.66
3.90
10.6
4.3
7.07
5.5
0.69
S
S
Oax
Oeq
–
–
–
94
6
6.7
10.1
Weighted[a]
6.4
11.8
1.7
5.8
6 trans
6.6[b]
7.1
−11.3
−8.5
−8.2
–
−13.2
−10.4
−9.0
–
10.6
12.1
0.8
3.3
1.35
11.1
2.0
5.9
3.9
8.4
4.2
7.0
5.5
6.9
5.6
–
–
–
S
S
Oax
Oeq
93
7
6.2
Weighted[a]
7.0
11.3
7 cis
−12.4
−9.4
−9.4
−7.0
−10.2
–
6.7[b]
6.55
6.8
−13.4
−11.0
−10.7
−9.8
−10.3
–
–
–
–
–
–
–
6.1
0.8
–
–
–
–
–
–
7.0
8.1
5.5
5.9
5.4
6.3
–
–
–
–
–
S
S
S
S
Oax(1)
Oax(2)
Oeq(1)
Oeq(2)
30
27
21
22
1.1
6.0
10.55
10.85
5.1
6.1
Weighted[a]
6.4
8 trans
−12.4
−9.3
−7.2
–
6.7[b]
6.1
−13.3
−10.0
−9.0
–
11.3
11.35
0.8
–
–
–
–
4.6
3.7
7.6
3.9
–
–
–
–
–
–
S
S
Oax
Oeq
95
5
6.4
Weighted[a]
6.1
10.8
9 cis
−12.4
−9.3
−6.95
–
−11.4
−8.2
−8.6
6.9[b]
6.3
11.4
10.2
1.1
–
–
–
–
–
–
–
–
5.9
5.2
4.9
5.2
–
–
–
S
S
Oax
Oeq
94.5
5.5
6.5
Weighted[a]
6.3
9.7
10 trans
−12.4
−9.7
−6.9
–
−11.4
−8.4
−8.1
–
7.3[b]
6.7
–
–
–
–
2.54
1.2
5.4
4.5
7.0
4.6
–
–
–
–
–
–
–
–
S
S
Oax
Oeq
95.5
4.5
6.2
11.0
1.6
Weighted[a]
6.7
[a] Weighted after Boltzmann. [b] Coupling with methyl group.
12
10
8
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
6
4
2
0
2
4
6
8
10
12
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
1
1
Computed H - H coupling constant / Hz
Computed 1H chemical shifts / ppm
Figure 2. The experimental vicinal 1H-1H coupling constants of com-
pounds 4–10 against the weighted computed ones. Jexp = (0.89
0.04)Jcomp + (1.32 0.28); R = 0.973, P < 0.0001.
Figure 3. The experimental 1H NMR chemical shifts of compounds 4–10
against the weighted computed ones. δexp = (0.86 0.04)δcomp + (0.48
0.14); R = 0.960, P < 0.0001.
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Magn. Reson. Chem. 2011, 49, 443–449
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
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K. Pihlaja et al.
13C. The spectra were taken in 5 mm o.d. tubes in CDCl3 using
internalTMSasreference.The90degreepulseswerethefollowing:
5.5 µs for 1H and 9 µs for 13C. Eight scans were accumulated for
1H and 300 for 13C. Temperature was kept constant at 303 1 K
during all the measurements. Resolution enhancement (1H; digital
resolution usually 32 and sometimes 64 k) and off-resonance (13C)
experiments were utilized when needed. The 1H spectra were
always practically first order although their analyses were in most
cases also confirmed by simulations.
70
60
50
40
30
20
10
Computations
The quantum chemical calculations were performed using the
Gaussian 03 program package.[14] The conformational analysis of
themoleculesandallgeometryoptimizationsweredoneincluding
the Møller-Pleset correlation energy correction, truncated at
second-order (MP2)[15]. Dunning’s[16] augmented, correlation
consistent triple-zeta basis set was used. Additionally, for all
computations, the Self-Consisted Reaction Field with the Polarized
Continuum Model using the Integral Equation Formalism (SCRF
IEF-PCM)[17] was applied to take the solvent effect of CHCl3
(ε = 4,8) into account. Chemical shift and coupling constants
were computed applying the GIAO formalism[18]. The reference
for the magnetic shielding was tetramethylsilane (TMS). The 13C
value of TMS was 199.05 ppm and the 1H value 31.61 ppm on the
used level of theory (MP2/aug-cc-pVTZ; solvent model: IEF-PCM
CHCl3). The computation of coupling constants were take place at
the B3LYP-DFT level of theory[19] used the Dunning’s aug-cc-VTZ
basis set. The results were displayed using the molecular modeling
0
10
20
30
40
50
60
70
80
Computed 13C chemical shifts / ppm
Figure 4. The experimental 13C NMR chemical shifts of compounds 4–10
againsttheweightedcomputedones.δexp = (0.96 0.02)δcomp +(−0.32
1.03); R = 0.994, P < 0.0001.
benzene-petroleum ether, bp 40–60 ◦C, 4 + 1 + 3), the stripe was
removedandelutedwithacetonewhichbythenevaporationgave
1.18 g (60.3%) 4 as colourless oil. Anal. Calcd for C3H6OS2 (122.2):
C 29.48, H 4.95, S 52.47%. Found C 29.28, H 4.90, S 52.64%.
Preparation of 1-oxo-2-methyl-1,3-dithiolanes (5 and 6)
1.92 g (16 mmol) 2 was oxidized with 2.80 g NaIO4 as described
for 4. From the product (2.1 g), the compound 6 was crystallized
with ether-petroleum ether (1 + l) standing overnight at −20 ◦C.
Colourless crystals (0.6 g, 27.5%), mp 49–50 ◦C from EtOH (lit.[2]
mp 48–49 ◦C). Anal. Calcd for C4H8OS2 (136.24) C 35.26, H 5.92,
S 47.07. Found C 35.45, H 5.70, S 47.28%. From an other mixture,
the oxidation product 5 was separated by preparative TLC. The
upper band on the plate was removed and extracted with acetone.
After evaporation, the solid obtained 0.93 g (42%) was crystallized
from ether-petroleum ether (bp 40–60 ◦C, 1 + 1), which standing
on cool gives 5. Colourless crystals, mp 48–49 ◦C. Anal. Calcd for
C4H8OS2 (136.24) C 35.26, H 5.92, S 47.07. Found C 35.51, H 5.70, S
47.18%.
software SYBYL[20]
.
Acknowledgements
The Academy of Finland and Finnish Cultural Foundation are
thanked for the financial support (JS).
Supporting information
Supporting information may be found in the online version of this
article.
Preparation of 1-oxo-4-methyl- (7 and 8) and -5-methyl-1,3-
dithiolanes (9 and 10)
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1.92 g (16 mmol) 4-methyl-1,3-dithiolane (3) was oxidized as
described for 4. The oily product obtained (1.98 g) was chro-
matographed on preparative silica gel TLC plates (1 mm) with
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(136.24) C 35.26, H 5.92, S 47.07. Found C 35.44, H 5.80, S 47.16%.
NMR measurements
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Magn. Reson. Chem. 2011, 49, 443–449

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Magn. Reson. Chem. 2011, 49, 443–449
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
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