A facile preparation of modified hydrophilic azulene derivatives

Article abstract of DOI:10.1016/j.tetlet.2013.04.039

A simple procedure was developed for the preparation of hydrophilic azulene derivatives from an abundant and commercially available source of guaiazulene sodium sulfonate 1. This protocol may open up an efficient route for the preparation of a series of hydrophilic azulene derivatives.

Full text of DOI:10.1016/j.tetlet.2013.04.039

Tetrahedron Letters 54 (2013) 3204–3206
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A facile preparation of modified hydrophilic azulene derivatives
⇑
Koichi Sato , Minyue Zhu, Naoko Takenaga
Department of Chemical Science and Technology, Faculty of Bioscience and Applied Chemistry, Hosei University, Kajino-cho 3-7-2, Koganei, Tokyo 184-8584, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple procedure was developed for the preparation of hydrophilic azulene derivatives from an abun-
dant and commercially available source of guaiazulene sodium sulfonate 1. This protocol may open up an
efficient route for the preparation of a series of hydrophilic azulene derivatives.
Received 25 February 2013
Revised 10 April 2013
Accepted 11 April 2013
Available online 24 April 2013
Keywords:
Guaiazulene
Hydrophilic
Sulfonate
Aldehyde
Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved.
Guaiazulene is a known active component of the essential oil of
Guaiacum officinalis L., and it has been used as an anti-allergenic-
and anti-inflammatory agent for many years.1 Guaiazulene is an
FDA-approved cosmetic color additive and has potential applica-
tions as a pharmaceutical. Of these, guaiazulene sodium sulfonate
1 (Fig. 1), a hydrophilic guaiazulene derivative, has found wide-
spread use in clinical applications as an anti-inflammatory and
anti-ulcer agent.2 Guaiazulene and its derivatives have been
obtained by the dehydrogenation of hydroazulene sesquiterepenes
of plant origin, which are more readily available than other synthe-
sized azulene compounds. Structurally similar hydrophilic
azulenes, such as KT1-32 (Fig. 1) are also used as anti-ulcer drugs.3
Their preparation is fairly different from that of guaiazulenes.
Hydrophilic azulenes are generally synthesized by introducing
hydrophilic moieties after multistep construction of azulene
nucleus from troponoids or phenols.4 Thus the preparation of
derivatives with greater structural diversity involves an
inconvenient conversion sequence.4c
Sulfonation is a critical reaction utilized to impart water-solu-
bility to hydrophobic molecules.5 Sulfonate salts of active pharma-
ceutical ingredients are particularly useful in the pharmaceutical
industry. The poor solubility of sulfonated molecules in most
organic solvents complicates their synthesis and purification, thus
relegating this modification to the final synthetic step in most
cases. Thus, appropriate protection of sulfonate is important.
Over the past few decades, we have investigated the develop-
ment of convenient and safe methods for synthesizing azulene
derivatives from guaiazulene.6 In continuation of our study, we
set out to explore the utility of readily available, mass-produced
1 as a starting material. To the best of our knowledge, synthetic
conversion of 1 into compounds with versatile applicability has
been rarely reported thus far.7,8 1 consists of an azulene ring with
a 1,4,7-alkyl side-chain and a 3-substituted sodium sulfonate
group. We envisaged the conversion of the alkyl group of 1 into a
functional group such as the formyl group, thus providing a direct
pathway to hydrophilic azulenes.
Aryl aldehydes are important industrial materials and serve as
principal synthetic intermediates in the production of dyes,
agricultural chemicals and pharmaceuticals.9 General oxidation
of aromatic alkyl groups into aryl aldehydes is well known in the
literature. In the field of azulene chemistry, the oxidation of alkyl
side-chain in azulenes is not easy since the azulene nucleus is
sensitive to oxidation reagents, such as chromic acid, nitric acid,
and permanganate.10,11 Kurokawa and co-workers reported that
oxidation of the 1-methyl group of guaiazulene into a formyl group
using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), pro-
ceeded only if an appropriate substituent was introduced at the
3-position.11b As a pilot experiment, we attempted direct oxidation
of sulfonate 1 by DDQ, but it is not successful.
SO3Na
SO3Na
KT1-32
guaiazulene
sodium sulfonate
guaiazulene
(anti-ulcer drug)
1
⇑
Corresponding author. Tel.: +81 42 387 6127; fax: +81 42 387 7002.
E-mail address: sato@hosei.ac.jp (K. Sato).
Figure 1. Pharmaceutically active azulenes.
0040-4039/$ - see front matter Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.04.039

K. Sato et al. / Tetrahedron Letters 54 (2013) 3204–3206
3205
Table 1
Protection of sulfonate 1
reduces the complicacies of treatment and purification in further
transformations.
With protected sulfonates in hand, we turned our attention to-
ward oxidation of 1-methyl groups of 4a–4c. DDQ-oxidation of
alkyl group of azulene is a common reaction,11 but its application
to azulene bearing sulfonate moiety was not examined so far. To
a solution of 4 in acetone–water was added 2.2 equiv of DDQ at
room temperature. To our delight, the desired aldehydes 5a–5c
were obtained in 51–55% yields (Scheme 1).13
(i)
(ii)
SO3Na
SO2Cl
SO2R
1
2
3 or 4
Entry
RH
Product
Methoda
Time (h)
Yield (%)
We have ascertained that prepared aldehydes 514 could be
applied to various transformations as presented in Scheme 2.15
Knoevenagel condensation and Michael addition proceeded
smoothly to afford the corresponding azulenes 6a–6e.16,17
1
2
3
4
5
6
7
8
n-PrNH2
i-PrNH2
NH2OHÅHCl
3a
3b
3c
3d
4a
4b
4c
4d
A
A
A
A
B
B
B
B
1.5
2.5
1.5
1.5
1
2
2.5
2.5
72 (31)b
62 (34)b
62
p-MeOC6H5NH2
MeOH
89
67
80
69
Azulenes bearing an a
-amino phosphonate18,19 or a sulfonylimino
EtOH
i-PrOH
C6H5CH2OH
moiety20,21 were also obtained. In the course of these transforma-
tions, hydrolysis of the sulfonic ester moieties was not observed,
demonstrating that appropriately protected 5 is a suitable precur-
sor for various hydrophilic azulene derivatives. Notably the
deprotection of these modified sulfonate esters proceeded
smoothly under mild condition (Scheme 3).22
45
a
Method A; (i) (COCl)2, DMF, Et2O, 0 °C, 10 min. (ii) Amine (RH), Na2CO3Å10H2O,
5 °C. Method B; (i) (COCl)2, DMF, DCM, 0 °C, 10 min. (ii) Alcohol (RH), pyridine, rt.
Yields in parentheses are literature yields reported in Ref. 7 and have been
provided for comparison. Reaction conditions described in Ref. 7 are as follows; (i)
b
(COCl)2, cat. DMF, DCM, pyridine, 0 °C, 10 min. (ii) Amine, Et3N, pyridine.
Evidently, suitable protection of the sulfonate moiety of 1,
which enables 1 to be stable under various reaction conditions
and to be deprotected easily after reactions, is needed. Herein we
demonstrate a simple transformation of 1 into aldehyde 5 (vide
infra), enabling the preparation of various hydrophilic azulenes
bearing a functionalized side-chain.
Z
X
O
O
O
HN
P
OEt
OEt
Initially we attempted a one-pot protection of sulfonate 1
through in situ generation of sulfonyl chloride 2. Recently, an
analogous approach was described by Yin and co-workers, but
the reaction condition was not examined in detail despite low
yields (20–48%).7 Thus, we evaluated to establish whether in situ
(d)
i
(a)
SO3 Pr
SO3Me
6a (X = Me): 83%
6b (X = OEt): 95%
CHO
6f (Z = OMe): 74%
6g (Z = Cl): 70%
generation of sulfonyl chloride 2 (Table 1) was possible.12
A
solution of oxalyl chloride in ether was dropped slowly into a stir-
red solution of 1 and DMF in ether, which was maintained at 0 °C.
After 10 min, n-propylamine and Na2CO3Å10H2O were added to
afford the desired sulfonamide 3a in 72% yield (entry 1). The yields
in parentheses in Table 1 demonstrated some improvement on
yields in the literature.7 Other amines were suited to the reaction
and gave 3b–3d in moderate to good yields (entries 2–4). Once a
clear in situ generation of sulfonyl chloride 2 was established, we
proceeded to prepare the sulfonate ester instead of sulfonamide
by considering facile deprotection after functionalization. In situ
treatment of sulfonyl chloride 2 with methanol afforded the corre-
sponding sulfonate ester 4a in 67% yield (entry 5). Alcohols that are
commonly used in industries, such as ethanol and isopropanol also
produced sulfonate esters 4b and 4c in 80% and 69% yields, respec-
tively, (entries 6–7), and the use of benzylic alcohol yielded the
poorest conversion (entry 8). We confirmed that the procedure
reported by Yin7 was not suitable for the preparation of these sul-
fonate esters. Thus, we have established a useful procedure for
conversion of hydrophilic 1 into sulfonate ester 4a–4d, which
(b)
SO2R
Y
O
(e)
5
S
CN
N
(c)
O
i
SO3 Pr
NH2
SO3Me
6c (Y = CN): 65%
O
CN
6h: 20%
6d (Y = CO2Et): 89%
i
SO3 Pr
6e: 69%
Scheme 2. Various transformations from 5. Reagents and conditions: (a) 5c
(1.0 equiv), pentane-2,4-dione (1.0 equiv) or ethyl-3-oxobutanoate (1.6 equiv),
Yb(OTf)3 (0.1 equiv), Ac2O (2.0 equiv), CH3NO2, 18 h, rt. (b) 5c (1.0 equiv), malo-
nonitirile (2.0 equiv) or 2-ethoxyacetonitrile (2.0 equiv), cat. piperidine, EtOH, 1 h,
rt. (c) 5c (1.0 equiv), malononitirile (1.0 equiv), dimedone (1.0 equiv), piperidine
(0.1 equiv), DCM, 24 h, reflux. (d) 5a (1.0 equiv), 4-methoxyaniline (1.0 equiv) or 4-
chloroaniline (1.0 equiv), diethyl phosphite (1.0 equiv), Sc(OTf)3 (0.1 equiv), THF,
24 h, rt. (e) 5a (1.0 equiv), (R)-(+)-2-methylpropane-2-sulfinamide (1.0 equiv),
CuSO4 (1.5 equiv), DCM, 18 h, rt.
CHO
DDQ (2.2 equiv)
2M NaOH
acetone, H2O
r.t.
SO2R
SO2R
(R = OMe)
EtOH (0.05M)
5a
5b
5c
(R = Me): 51% (1 h)
(R = OEt): 52% (2 h)
(R = O Pr): 55% (2.5 h)
4a
4b
4c
reflux, 1 h
: modified moiety
Scheme 3. Deprotection of sulfonate ester 6.
SO3Na
SO2R
6
(R = OEt)
i
(R = O Pr)
R = OMe, OiPr
i
Scheme 1. Oxidation of 1-methyl group of 4 by DDQ.

3206
K. Sato et al. / Tetrahedron Letters 54 (2013) 3204–3206
(2.2 mmol) was added at room temperature. The resultant mixture was
In summary, the facile synthesis of hydrophilic azulene deriva-
extracted with chloroform, washed with water, dried over anhydrous sodium
sulfate, and concentrated. The residue was purified by silica gel column
chromatography (3:1 hexane–acetone as eluent) to give 5c as red prisms (55%).
mp: 133 °C. 1H NMR(CDCl3) d:1.32 (6H, d, J = 6.0 Hz), 1.44 (6H, d, J = 6.8 Hz),
3.28 (1H, sep, J = 6.8 Hz), 3.42 (3H, s), 4.86 (1H, sep, J = 6.0 Hz), 7.82 (1H, d,
J = 10.8 Hz), 7.91 (1H, dd, J = 2.0, 10.8 Hz), 8.74 (1H, s), 10.10 (1H, d, J = 2.0 Hz),
10.24 (1H, s). MS: calcd for C18H22O4S: 334.1239, found: 334.3614.
14. The reactivity of sulfonylazulene carbaldehydes is quite different due to the
electron-withdrawing sulfonyl group and their poorer solubility. The
protection of the sulfonyl group is plausible for the effective transformations.
15. There are a number of synthetic reports of azulene hybrid compounds for the
purpose of their numerous applications (a) Razus, A. C.; Nitu, C.; Tecuceanu, V.;
Cimpeanu, V. Eur. J. Org. Chem. 2003, 4601; (b) Razus, A. C.; Birzan, L.;
Tecuceanu, V.; Cristea, M.; Nicolescu, A.; Enache, C. Rev. Roum. Chim. 2007, 52,
189; (c) Shoji, T.; Ito, S.; Toyota, K.; Yasunami, M.; Morita, N. Chem. Eur. J. 2008,
14, 8398.
tives bearing a range of functional groups is demonstrated.23 The
selection of sulfonate esters as protecting groups was prompted
by the evaluation of their properties, namely, their stability toward
various reaction conditions and the ease with which they may be
cleaved to create hydrophilic forms under mild conditions, thereby
providing access to preparative routes for a diverse range of hydro-
philic azulenes. Related products described herein may be useful
intermediates for the development of pharmacologically active
agents containing the azulene skeleton. The facile and efficient
synthesis of other azulene derivatives is now in progress in our
laboratory.
16. (a) Kaupp, G.; Naimi-Jamal, M. R.; Schmeyers, J. Tetrahedron 2003, 59, 3753; (b)
Abdolmohammadi, S.; Balalaie, S. Tetrahedron Lett. 2007, 48, 3299; (c) Khurana,
J. M.; Nand, B.; Saluja, P. Tetrahedron 2010, 66, 5637.
References and notes
1. Yamazaki, H.; Irono, S.; Uchida, A.; Ohno, H.; Saito, N.; Kondo, K.; Jinzenji, K.;
Yamamoto, T. Nippon Yakurigaku Zasshi 1958, 54, 362.
2. Okabe, S.; Takeuchi, K.; Honda, K.; Ishikawa, M.; Takagi, K. Oyo Yakuri 1975, 9,
31.
3. (a) Okabe, S.; Takeuchi, K.; Mori, Y.; Furukawa, O.; Yamada, Y. Nippon
Yakurigaku Zasshi 1986, 88, 467; (b) Suzaka, H.; Takeshita, M.; Sato, M.;
Tomiyama, T.; Miyazaki, H. Yakubutudotai 1990, 5, 217.
4. (a) Yanagisawa, T.; Wakabayashi, S.; Tomiyama, T.; Yasunami, M.; Takase, K.
Chem. Pharm. Bull. 1988, 36, 641; (b) Yanagisawa, T.; Kosakai, K.; Tomiyama, T.;
Yasunami, M.; Takase, K. Chem. Pharm. Bull. 1990, 38, 3355; (c) Yanagisawa, T.;
Kosakai, K.; Izawa, C.; Tomiyama, T.; Yasunami, M. Chem. Pharm. Bull. 1991, 39,
2429; (d) Kane, J. L., Jr.; Shea, K. M.; Crombie, A. L.; Danheiser, R. L. Org. Lett.
2001, 3, 1081.
17. A typical procedure for Knoevenagel condensation and Michael cyclization
(Scheme 2): to
a stirred solution of 5c (0.20 mmol) in DCM (5 mL),
malononitrile (0.20 mmol), dimedone (0.20 mmol), and piperidine
(0.02 mmol) were added and refluxed for 24 h. The resultant mixture was
extracted with chloroform, washed with water, dried over anhydrous sodium
sulfate, and concentrated. The residue was purified by silica gel column
chromatography (2:1 hexane–ether as eluent) to give 6e as purple needles
(69%). mp: 131 °C. 1H NMR(CDCl3) d:1.03 (3H, s), 1.12 (3H, s), 1.24 (6H, t,
J = 6.4 Hz), 1.45 (6H, dd, J = 2.0, 6.8 Hz), 2.13–2.24 (2H, m), 2.44–2.57 (2H, m),
3.21 (1H, sep, J = 6.8 Hz), 3.31 (3H, s), 4.53 (2H, s), 4.66 (1H, sep, J = 6.4 Hz),
5.07 (1H, s), 7.46 (1H, d, J = 11.2 Hz), 7.67 (1H, dd, J = 2.0, 11.2 Hz), 8.07 (1H, s),
8.86 (1H, s). MS: calcd for C29H34N2O5S: 522.2188, found: 522.2940.
18. (a) Atherton, F. R.; Hassall, C. H.; Lambert, R. W. J. Med. Chem. 1986, 29, 29; (b)
Kukhar, V. P.; Solodenko, V. A. Russ. Chem. Rev. 1987, 56, 859; (c) Qian, C.;
Huang, T. J. Org. Chem. 1998, 63, 4125; (d) Ranu, B. C.; Hajra, A.; Jara, U. Org. Lett.
1999, 1, 1141.
5. (a) Teasdale, A.; Delaney, E. J.; Eyley, S. C.; Jacq, K.; Worth, K. T.; Lipczynski, A.;
Hoffmann, W.; Reif, V.; Elder, D. P.; Facchine, K. L.; Golec, S.; Oestrich, R. S.;
Sandra, P.; David, F. Org. Process Res. Dev. 2010, 14, 999; (b) Miller, S. C. J. Org.
Chem. 2010, 75, 4632; (c) Pauff, S. M.; Miller, S. C. Org. Lett. 2011, 13, 6196; (d)
Pauff, S. M.; Miller, S. C. J. Org. Chem. 2013, 78, 711.
19.
A typical procedure for the preparation of azulenes bearing an a-amino
phosphonate group (Scheme 2): to a stirred solution of 5a (0.75 mmol) in THF
(5 mL), 4-methoxyaniline (0.75 mmol), diethyl phosphite (0.75 mmol), and
Sc(OTf)3 (0.075 mmol) were added at room temperature and stirred for 24 h.
The resultant mixture was extracted with chloroform, washed with water,
dried over anhydrous sodium sulfate, and concentrated. The residue was
purified by silica gel column chromatography (1:1 hexane–acetone as eluent)
to give 6f as purple prisms (74%). mp: 156 °C. 1H NMR(CDCl3) d:1.08 (3H, t,
J = 7.0 Hz), 1.28 (3H, t, J = 7.0 Hz), 1.37 (6H, t, J = 7.0 Hz), 3.14 (1H, sep,
J = 6.9 Hz), 3.30 (3H, s), 3.67 (6H, s), 3.75–3.82 (1H, m), 3.97–4.03 (1H, m),
4.07–4.16 (2H, m), 4.41 (1H, t, J = 7.8 Hz), 5.28 (1H, dd, J = 7.2, 22.4 Hz), 6.55
(2H, d, J = 8.8 Hz), 6.65 (2H, d, J = 9.2 Hz), 7.52 (1H, d, J = 11.2 Hz), 7.69 (1H, dd,
J = 2.0, 11.2 Hz), 8.43 (1H, d, J = 2.4 Hz), 8.65 (1H, d, J = 2.0 Hz). MS: calcd for
6. (a) Sato, K.; Yamaguchi, M.; Ogura, I. Nippon Kagaku Kaishi 1982, 1199; (b) Sato,
K.; Arifuku, N.; Takigawa, T. Abstracts of papers, the 45th Symposium on the
Chemistry of Terpenes, Essential Oils, and Aromatics, October 2001,p. 162.; (c)
Sato, K.; Nakagawa, K.; Ozu, T. Abstracts of papers, the 90th Annual Meeting of
the Chemical Society of Japan, Osaka, March 2010, 2PB-068.; (d) Sato, K.; Ozu,
T.; Takenaga, N. Tetrahedron Lett. 2013, 54, 661; (e) Sato, K.; Yokoo, E.;
Takenaga, N. Heterocycles 2013, 87, 807.
7. A simple modified guaiazulene sulfonamide derivative demonstrated excellent
in vivo anti-gastric ulcer activity. See; Zhang, L.-Y.; Yang, F.; Shi, W.-Q.; Zhang,
P.; Li, Y.; Yin, S. F. Bioorg. Med. Chem. Lett. 2011, 21, 5722.
8. Hamajima, R.; Iwano, K.; Okuda, H. Yakugaku Zasshi 1978, 98, 1101.
9. Bruhne, F.; Wright, E. In Industrial Organic Chemicals: Starting Materials and
Intermediates-Ullmann’s Encyclopedia; Wiley-VCH: Weinheim, 1999; Vol. 2, pp
673–692.
10. (a) Treibs, W. Chem. Ber. 1957, 90, 761; (b) Treibs, W.; Vogt, R. Chem. Ber. 1961,
94, 1739; (c) Kohara, K. Bull. Chem. Soc. Jpn. 1969, 42, 3229.
C27H36NO7PS: 549.1950, found: 549.2579.
20. Liu, G.; Cogan, D. A.; Owens, T. D.; Tang, T. P.; Elleman, J. A. J. Org. Chem. 1999,
64, 1278.
21. A typical procedure for the synthesis of azulenes bearing a sulfonylimino group
(Scheme 2): to a stirred solution of 5a (0.50 mmol) in DCM (3 mL), (R)-(+)-2-
methylpropane-2-sulfinamide (0.50 mmol), CuSO4 (0.75 mmol) were added at
room temperature and stirred for 18 h. The resultant mixture was extracted
with dichloromethane, washed with water, dried over anhydrous sodium
sulfate, and concentrated. The residue was purified by silica gel column
chromatography (4:1 hexane–acetone as eluent) to give 6h as red prisms
(20%). mp: 150 °C. 1H NMR(CDCl3) d:1.31 (9H, s), 1.42 (6H, dd, J = 2.8, 7.2 Hz),
3.22 (1H, sep, J = 6.9 Hz), 3.37 (3H, s), 3.85 (3H, s), 7.73 (1H, d, J = 11.2 Hz), 7.85
(1H, dd, J = 2.4, 11.2 Hz), 8.71 (1H, s), 9.00 (1H, s), 9.82 (1H, d, J = 2.0 Hz). MS:
calcd for C20H27NO4S2: 409.1381, found: 409.4801.
22. (a) Lum, R. T.; Cheng, M.; Cristobal, I. D.; Evans, J. L.; Keck, J. G.; Macsata, R. W.;
Manchem, V. P.; Matsumoto, Y.; Park, S. J.; Rao, S. S.; Robinson, L.; Shi, S.;
Spevak, W. R.; Schow, S. J. Med. Chem. 2008, 51, 6173; (b) Lourenco, N. M. T.;
Monteiro, C. M.; Afonso, C. A. Eur. J. Org. Chem. 2010, 6938.
23. Typically, sulfonylation of azulenes bearing electron-donating groups can
smoothly proceed (see Refs. 4,7). However, in the case of the electron-deficient
carbonylazulenes in this study, introduction of sulfonate moiety into azulene
ring in the last step did not smoothly proceed and requires very harsh
conditions. In this point, our procedure starting from the sulfonylated azulene
has some advantages.
11. (a) Amemiya, T.; Yasunami, M.; Takase, K. Chem. Lett. 1977, 587; (b) Okajima,
T.; Kurokawa, S. Chem. Lett. 1997, 69; (c) Backer, D. A. J. Am. Chem. Soc. 1996,
118, 905.
12. We found that the addition of extra pyridine adversely affected this reaction. A
typical procedure for the preparation of sulfonate esters: (Table 1, entry 7): To
a
stirred solution of
1
(10 mmol) and DMF (1.2 mL) in dichloromethane
solution of oxalyl chloride (25 mmol) in
(50 mL), maintained at 0 °C,
a
dichloromethane (10 mL) was added slowly, and the resultant solution was
stirred at the same temperature. After 10 min, isopropanol (10 mL) and
pyridine (2 mL) were added and the mixture stirred for 2.5 h. After the reaction
was completed, the resultant mixture was extracted with dichloromethane,
washed with aqueous sodium hydroxide, dried over anhydrous sodium sulfate,
and concentrated. The residue was purified by silica gel column
chromatography (6:1 hexane–ether as eluent) to give 4c as purple prisms
(69%) mp: 99 °C. 1H NMR(CDCl3) d: 1.27 (6H, d, J = 6.0 Hz), 1.39 (6H, d,
J = 6.8 Hz), 2.59 (3H, s), 3.15 (1H, sep, J = 6.8 Hz), 3.33 (3H, s), 4.74 (1H, sep,
J = 6.0 Hz), 7.42 (1H, d, J = 11.1 Hz), 7.62 (1H, d, J = 11.1 Hz), 8.19 (1H, s), 8.31
(1H, s). MS: calcd for C18H24O3S: 320.1446, found: 320.1565.
13. A typical procedure for the oxidation by employing DDQ (Scheme 1): to a
stirred solution of 4c (1.0 mmol) in acetone/water (9:1, 50 mL), DDQ