Synthetic studies on 2H-Thiopyran compounds: A reinvestigation of the reaction between benzaldehydes and sodium sulfide

Article abstract of DOI:10.1080/10426500902717523

An investigation regarding the synthesis of 2H-thiopyran compounds from substituted benzaldehydes with sodium sulfide (Na₂S10H₂O) in aqueous ethanol was carried out. The structural elucidation of the products was performed by spectro

Full text of DOI:10.1080/10426500902717523

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Phosphorus, Sulfur, and Silicon
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Synthetic Studies on 2H-
Thiopyran Compounds: A
Reinvestigation of the Reaction
Between Benzaldehydes and
Sodium Sulfide
a
a
Avijit Banerji , Pizush Kanti Biswas , Debasish
a
a
b
Bandyopadhyay , Maya Gupta , Thierry Prangé
&
b
Alain Neuman
a
Centre of Advanced Studies on Natural Products
Including Organic Synthesis, Department of
Chemistry, Calcutta University, Kolkata, India
b
Centre Universitaire, Paris-sud, Batiment 209D-
BP34, Orsay Cedex, France
Published online: 18 Nov 2009.
To cite this article: Avijit Banerji , Pizush Kanti Biswas , Debasish Bandyopadhyay ,
Maya Gupta , Thierry Prangé & Alain Neuman (2009): Synthetic Studies on 2H-
Thiopyran Compounds: A Reinvestigation of the Reaction Between Benzaldehydes and
Sodium Sulfide, Phosphorus, Sulfur, and Silicon and the Related Elements, 184:12,
3199-3211
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Phosphorus, Sulfur, and Silicon, 184:3199–3211, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902717523
Synthetic Studies on 2H-Thiopyran Compounds: A
Reinvestigation of the Reaction Between Benzaldehydes
and Sodium Sulfide
1
1
Avijit Banerji, Pizush Kanti Biswas,
1
1
Debasish Bandyopadhyay, Maya Gupta,
Thierry Prang e´ , and Alain Neuman
Centre of Advanced Studies on Natural Products Including Organic
Synthesis, Department of Chemistry, Calcutta University, Kolkata,
India
2
2
1
2
Centre Universitaire, Paris-sud, Batiment 209D-BP34, Orsay
Cedex, France
An investigation regarding the synthesis of 2H-thiopyran compounds from substi-
tuted benzaldehydes with sodium sulfide (Na2S·10H2O) in aqueous ethanol was
carried out. The structural elucidation of the products was performed by spectro-
scopic methods and in one example as X-ray crystallographic analysis. A plausible
mechanistic pathway is also proposed that is entirely different from an earlier
report.
Keywords Benzaldehyde; microwave irradiation; NMR; sodium sulfide; 2H-thiopyran;
X-ray crystallography
INTRODUCTION
Sulfur chemistry constitutes a major branch of organic chemistry,
among which thiopyran compounds in particular possess enormous
medicinal, as well as biological and industrial, importance. Thiopyran
1
compounds have a wide range of applications such as sensitizers, key
2
3
4
intermediates for pharmaceuticals, insecticides, herbicides, polymer
Received 28 October 2008; accepted 30 December 2008.
The authors thank the Indian Council for Cultural Relation (ICCR) for financial as-
sistance to P. K. Biswas.
The present affiliation for P.K.B. is BCSIR Laboratory, Dhanmondi, Dhaka,
Bangladesh.
The present affiliation for D.B. is Department of Chemistry, The University of
Texas–Pan American, Edinburg, Texas, USA.
Address correspondence to Avijit Banerji, Centre of Advanced Studies on Natural
Products Including Organic Synthesis, Department of Chemistry, Calcutta University,
92 Acharya Prafulla Chandra Road, Kolkata 700009, India. E-mail: ablabcu@yahoo.co.uk
3199

3200
A. Banerji et al.
5
2
6
initiator, plant protective agents, and juvenile hormones. Different
types of thiopyran compounds have been synthesized in the recent
7
–10
11–13
past.
However, except for a few cases,
2H-thiopyran compounds
1
4
have not yet been thoroughly investigated. Latif et al. reported that
when benzaldehyde reacted with sodium sulfide in aqueous ethanol,
it gave 3-benzyl-2,6-diphenyl-2H-thiopyran-5-carboxaldehyde in good
yield. Cremer and Subbaratnam15 proposed a probable mechanism
where cinnamaldehyde was postulated as an intermediate. Since it
has been found from our repeated experiments that cinnamaldehyde
itself failed to give the reaction, it was quite pertinent to reinvestigate
the reaction. Moreover, synthetic as well as mechanistic interests in
this reaction prompted us to take up a systematic study of new 2H-
thiopyran compounds using various substituted benzaldehydes. The
reactions were conducted to determine the factors involved in the prod-
uct formation as well as to extend the scope of the reaction. A microwave
irradiation technique has also been successfully used for carrying out
several of these reactions.
RESULTS AND DISCUSSION
Six aromatic aldehydes were used successfully as substrates viz. ben-
zaldehyde (1), 4-methylbenzaldehyde (3), 3- methylbenzaldehyde (5), 4-
methoxybenzaldehyde (7), 2-methoxybenzaldehyde (9), and veratralde-
hyde (11) (Scheme 1). 4-Chloro, 4-bromo, and 4-nitrobenzaldehyde,
however, failed to undergo the reaction. In all the reactions, thiopy-
ran compounds were the major products, and the yields were around
50–60%. Some of the corresponding benzoic acids and benzyl alcohols
SCHEME 1

Synthetic Studies on 2H-Thiopyran Compounds
3201
were also formed following a Cannizzaro reaction. The structures of
all the compounds were established by various spectroscopic analyses,
1
13
particularly FT-IR, 300 MHz H NMR, and 75.5 MHz C NMR. The
1
H NMR spectra of all the thiopyran compounds showed that olefinic
proton H-4 appeared at ∼δ 7.0 ppm, the benzylic proton H-2 adjacent to
the heteroatom appeared at ∼δ 4.5 ppm, whereas two benzylic proton
(
AB pattern), somewhat differentiated being near to a chiral center,
appeared in the region ∼δ 3–4 ppm.
The spectroscopic data of compound (4) are discussed below as a rep-
resentative example of this series. The structure of (4) was confirmed
finally by an X-ray crystallographic analysis.
The UV spectrum of (4) showed absorption maxima at 368 nm (log
ε: 3.79) and at 266 nm (log ε: 4.14), indicating the presence of extended
conjugation and aromatic ring, respectively. IR spectrum of (4) showed
−
1
strong absorption band at 1650 cm , indicating the presence of con-
−1
jugated carbonyl group. Medium intensity bands at 2916, 2852 cm
revealed the presence of –CH2 stretching. A weak absorption band
at 2743 cm showed the presence of H-CO group, whereas a strong
intensity band at 1206 cm indicated the presence of benzylic group,
and the absorption band at 819.5 cm indicated the presence of 1,4-
disubstituted benzene ring.
−1
−1
−
1
This structure was further supported by mass spectral fragmenta-
+
tion (4), which showed the expected M peak at m/z 410. Characteristic
+
+
peaks were obtained at m/z 381 [M −CHO], 319 [M −C6H4CH3], 305
+
[
M −CH3C6H4CH2], 277 [305—CO].
1
The 300 MHz H NMR spectrum of the compound (4) showed that
H-2 adjacent to the heteroatom appeared as singlet at δ 4.54 ppm,
while two other benzylic protons (AB pattern) near to a chiral cen-
ter were differentiated and appeared as doublets at δ 3.69 and 3.35
ppm (JAB = 15.2 Hz). The olefinic proton H-4 appeared as singlet at
δ 7.02 ppm, and the aldehyde proton as a singlet at δ 9.47 ppm. The
three methyl groups appeared as three singlets at δ 2.39, 2.38, and
2
.37 ppm. Twelve aromatic protons appeared in two sets of six dou-
blets at δ 7.26 ppm (J = 8.0 Hz) and δ 7.20 ppm (J = 8.0 Hz). Thus
it was clear that three 4-methylphenyl moieties were present and are
1
connected to the thiopyran ring system. From the H NMR shift of H-2
(
δ 4.54 ppm, singlet), it was reasonable to assume that one of these
aryl groups was present as S-CH-C6H4CH3–4 moiety in the thiopyran
ring. The molecule also contains a conjugated aldehyde group and one
olefinic proton. The 75.5 MHz 13C NMR assignments of compound (4)
showed the presence of one olefinic carbon at δ 119.7 ppm, two ben-
zylic carbons at δ 46.0 (methine) and 42.0 ppm (methylene), and three
methyl signals (δ 20.9, 20.91, and 21.1 ppm). The presence of eight

3202
A. Banerji et al.
FIGURE 1 X-ray crystallogaphic structure of 4 (ORTEP projection). Ellipsoids
are drawn at the 50% probability level, hydrogen atoms are given as open circles
with arbitrary radii.
quaternary carbons and six different types of aromatic methines
was evident from the comparison of fully decoupled spectrum with
DEPT-135. The most downfield carbon, obviously the carbonyl car-
bon, appeared at δ 186.0 ppm. Assignment of the aromatic carbon
of all the three rings “A,” “B,” and “C” could be made on the ba-
sis of intercomparison with the other products and the use of ad-
1
6
divitity parameters. From all these observations as well as the
1
4
structure of the compound reported earlier, it may be concluded
that the reaction of 4-methylbenzaldehyde with sodium sulfide in
aqueous ethanol gave 3-(4-methylbenzyl)-2,6-di(4-methylphenyl)-2H-
thiopyran-5-carboxaldehyde (4).
The structural features of the compound (4) were finally confirmed
by X-ray crystallographic analysis. Crystal data refinement parameters
are presented in Table I. The ORTEP projection is shown in Figure 1,
and some selected bond angles and lengths are presented in Table II.
The X-ray crystallographic analysis of (4) showed it to possess a six-
membered, sulfur-containing ring. As this ring is non-aromatic having
a diene moiety, it showed a rather important off-plane bending. As a
result the tolyl group at C(2) comes appreciable out of the plane.
The
carboxaldehyde (2) was proposed by Cremer and Subbaratnam
from the spectroscopic studies, and later was confirmed by X-ray
structure
of
3-benzyl-2,6-diphenyl-2H-thiopyran-5-
1
5

Synthetic Studies on 2H-Thiopyran Compounds
3203
TABLE I Crystal Structure and Data Refinement Parameters
for Compound 4
Compound
4
Empirical formula
Formula weight
C28H26OS
410.55
Crystal system/space group
P21/n
a/Å
b/Å
c/Å
12.351(2)
11.141(2)
17.193(2)
90
94.28(5)
90
2359.2(6)
4
1.156
◦
α/
◦
β/
◦
γ/
3
V/Å
Z
D calc (g/cm )
µ (mm
3
−1
)
0.153
Crystal size (mm)
Color/shape
Temp (K)
0.4 × 0.2 × 0.2
Yellowish
293
Theta range for collection
Reflections collected
Independent reflections
Data/restraints/parameters
2.10–29.82
12236
6138
2470 / 273
0.941
2
Goodness of fit on F
Final R indices [I > 2σ(I)]
R indices (all data)
0.0672
0.0880
Largest difference peak/hole
+0.21/–0.42
crystallography. In the mechanism proposed by Cremer and Subbara-
tram, the intermediacy of cinnamaldehyde was postulated. Since, it
has been found that cinnamaldehyde itself failed to give the reaction;
a modified scheme has been proposed (Scheme 2). It is proposed
that ArCH(SH)2 is reversibly formed from the arylaldehyde in the
−
reaction medium, which contains large amounts of SH ions. This then
participates in the reaction, as shown in Scheme 2.
Apart from the thermal synthesis of thiopyran compound,
a modified procedure applying microwave irradiation technique
was also explored. The reaction of some substituted benzalde-
hydes viz. 4-methylbenzaldehyde, 3-methylbenzaldehyde, and 2-
methoxybenzaldehyde to give corresponding thiopyran compounds also
yielded the same products under microwave irradiation conditions.
Yields were 50–60% after 30 min of microwave irradiation. 4-Chloro,
4-bromo, and 4-nitrobenzaldehyde again failed to give the thiopyran
compounds under microwave irradiation conditions.

3204
A. Banerji et al.
SCHEME 2

Synthetic Studies on 2H-Thiopyran Compounds
3205
◦
TABLE II Selected Bond Lengths (Å) and Angles ( ) for 4
S1
C2
C22
C24
C3
-C2
1.732 (6) S1
1.489 (8) C21
1.395 (8) C23
1.533 (9) C25
1.465 (7) C31
1.520 (7) C5
1.343 (8) C51
1.374 (10) C54
1.385 (8) C6
1.389 (7) C62
1.352 (9) C64
-C6
1.832 (6) C2
1.366 (7) C21
1.404 (8) C24
1.388 (8) C3
1.236 (7) C4
1.544 (7) C5A
1.356 (9) C52
1.377 (9) C54
1.532 (8) C61
1.389 (8) C63
-C3
1.375 (7)
1.415 (7)
1.363 (8)
1.426 (7)
1.323 (7)
1.533 (9)
1.407 (10)
1.517 (9)
1.368 (8)
1.382 (8)
1.392 (9)
-C21
-C23
-C241
-C4
-C5A
-C52
-C54
-C56
-C66
-C65
-C22
-C24
-C26
-O1
-C26
-C25
-C31
-C5
-C51
-C53
-C541
-C62
-C64
-C66
C5
-C6
C51
C53
C55
C61
C64
-C56
-C55
-C61
-C63
-C641 1.513 (9) C65
C2
C3
-S1
-C2
-C6
-S1
-C26
-C2
-C24
-C241
-C26
-C31
-C4
104.1 (3) C3
-C2
-C2
-C21
-S1
-C2
-C23
-C23
-C241 118.9 (6)
-C21
-C4
-C3
124.9 (5)
113.1 (4)
122.6 (5)
121.6 (5)
117.8 (6)
121.7 (4) C21
118.7 (6) C22
118.6 (5) C21
120.0 (6) C25
123.3 (6) C23
123.1 (6) C25
121.6 (5) C2
117.6 (5) O1
C22
C26
C22
C25
C24
C2
-C21
-C21
-C23
-C24
-C25
-C3
-C21
-C22
-C24
-C24
-C26
-C3
118.8 (5)
120.7 (5)
124.8 (6)
C31
-C3
-C31
In conclusion, a detailed study regarding the synthetic as well
as mechanistic aspects of the reaction between benzaldehydes with
sodium sulfide has been carried out which reveals that, first, 4-chloro,
4-bromo, and 4-nitrobenzaldehyde failed to undergo the reaction ei-
ther by the thermal procedure or the microwave irradiation technique.
Hence it can be concluded that the reaction does not occur with electron-
withdrawing substituents on the aromatic ring. It may be due to the
fact that the presence of strong –I group at the 4-position of benzalde-
hydes makes the aromatic ring much more electron deficient, and con-
sequently it becomes more reactive towards nucleophiles. Thus in spite
of producing the expected compound, it reacts differently to yield other
products following Cannizaro pathway. Second, cinnamaldehyde, pro-
posed earlier as an intermediate,14 also failed to undergo the reaction.
This clearly indicated the necessity to introduce a new mechanistic
pathway.
EXPERIMENTAL
Melting points were recorded on an electrically heated K o¨ fler Block ap-
paratus and are uncorrected. Column and thin layer chromatography
were carried out using silica gel (Qualigens 60–120 mesh, Spectrochem
60–120, and 100–200 mesh) and silica gel G (Spectrochem and SRL),

3206
A. Banerji et al.
respectively. Anhydrous sodium sulfate was used for drying extracts.
The analytical samples were routinely dried over CaCl2 in vacuo at
room temperature. The aldehydes used were A.R. reagents obtained
from Merck, Aldrich, and Spectrochem (India). Purities were checked
1
by H NMR spectroscopy. Sodium sulfide decahydrate (Na2S.10H2O)
obtained from Spectrochem (India) was used for these reactions. IR
spectra were recorded in KBr discs on a Perkin-Elmer RXI FT-IR spec-
trometer. UV spectra were measured on a Hitachi U-3501 spectropho-
tometer and the mass spectra (EI-MS) were recorded with a JEOL JMS
1
600 mass spectrometer. Elemental analyses (C, H, S) were conducted
using the Perkin-Elmer 2400 Series II elemental analyzer and results
were found to be in good agreement (± 0.2%) with the calculated values
for C, H, S. NMR spectra were usually recorded in CDCl3 solution on
a Bruker AM-300L at the Departmental facilities—a super conduct-
ing Oxford magnet NMR spectrometer (7.5 Tesla) equipped with an
ASPECT-3000 computer, an array processor, and a sophisticated pro-
cess controller. These spectra were recorded using a switchable 5 mm
1
13
H- C dual probes at ambient temperature and operating with the
Bruker DISR 861 and DISR 871 software. The spectrometer frequen-
1
cies in the Bruker AM-300L are 300.133 MHz for H NMR and 75.457
1
3
MHz for C NMR. Some spectra were also recorded with a Bruker DRX
00 NMR spectrometer (11.7 Tesla), equipped with a Silicon Graphics
5
INDY computer. These spectra were recorded in BBI (broad band in-
verse) probe with 5 mm NMR sample tube at 27 C temperature. The
◦
actual spectrometer frequencies are 500.134 MHz and 125.770 MHz,
1
13
respectively, for H and C NMR in the instrument. X-ray crystallo-
graphic data were recorded with an automatic NONIUS CAD-4 diffrac-
tometer. All recordings are at room temperature. X-ray crystallographic
data were recorded with an automatic NONIUS CAD-4 diffractometer.
The wavelength of MoKα radiation was 0.7107 Å. The structure were
solved by direct methods and refined with the SHELXL program.1
Data collection was performed at room temperature. The crystals were
monoclinic; space group P21/n. An ORTEP projection is shown in Fig-
ure 1. Crystallographic data for compound 4 have been deposited with
the Cambridge Crystallographic Data Centre as CCDC 248039. Copies
of the data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK (fax: +44 1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk).
7
General Method
The benzaldehyde or substituted benzaldehyde was taken with a 1:3
molar ratio of sodium sulfide in aqueous ethanol (1:1). The mixture

Synthetic Studies on 2H-Thiopyran Compounds
3207
was refluxed on an oil bath for 3–7 h with continuous stirring. The re-
1
actions were monitored by TLC and H NMR spectroscopy. The reaction
mixture was then cooled and kept standing overnight at room temper-
ature and then extracted with ether (3 × 50 mL). The post-reaction
mixture was concentrated under reduced pressure, and the residue
◦
was chromatographed over silica gel [petroleum ether (60–80 C)/
benzene].
Microwave Irradiation Assisted Procedure
The reactants, in the proportions mentioned above, were subjected to
microwave irradiation via a microwave oven (BMO-700T) operating at
a power of ∼1000 watts for 30 min. A modified apparatus with a reflux
condenser was used.
Reaction of Benzaldehyde (1) with Sodium Sulfide in Aqueous
Ethanol: 3-Benzyl-2,6-diphenyl-2H-thiopyran-5-
carboxaldehyde (2; C H SO)
2
5
20
Benzaldehyde (2.65 g, 0.025 mol) and sodium sulfide (18 g, 0.075 mol)
were reacted in aqueous ethanol (1:1, 100 mL) under reflux for 4 h. Col-
umn chromatography over silica gel [10% benzene in petroleum ether
◦
◦
(
60–80 C)] yields yellow crystals, mp 144 C; yield: 1.68 g (55%); IR: ν
=
2842.5 (m, CH2-), 1641.5 (s, aldehyde >C=O), 1208.5 (s, benzylic),
−1
7
33.5, 696.5 (m, monosubstituted benzene ring); cm ; UV: λmax (log ε) =
1
365.5 (4.15) and 267 (4.64) nm; H NMR (CDCl3, δ, 300 MHz): 4.54 (1H,
s, H-2), 7.02 (1H, s, H-4), 3.72 and 3.38 (1H, d, J = 15.2 each benzylic
1
3
methylene), 9.43 (1H, s, CHO), 7.34–7.27 (15H, m, H-A,B,C) ppm;
NMR (CDCl3, δ, 75.5 MHz): 46.2 (C-2), 138.3 (C-3), 120.0 (C-4), 154.5
C-5), 140.9 (C-6), 42.6 (−CH2-, benzylic), 186.5 (-CHO), 132.0 (A,C-
), 129.0 (A,C-2,6), 128.9 (A,C-3,5), 128.1 (A,C-4), 128.8 (B,C-1), 127.3
B,C-2,6), 128.2 (B,C-3,5), 126.7 (B,C-4), 133.9 (C,C-1), 131.1 (C,C-2,6),
C
(
1
(
+
+
1
29.1 (C,C-3,5), 130.3 (C,C-4) ppm: MS (EI): m/z = 368 (M ), 339 (M -
+
•
+−
+
•
CHO), 292 [M −C6H5 + H ], 277 [M
C6H5CH2 ], 247 (277—CHO-
•
+
•
+
H ), 215 [M −2C6H5 + H ], 121 (Ph-CS ), 91 (C7H7 ). Anal. Calcd. For
C25H20SO: C, 81.73; H, 5.50; S, 8.75, Found: C, 81.65; H, 5.44; S, 8.70.
Reaction of 4-Methylbenzaldehyde (3) with Sodium Sulfide in
Aqueous Ethanol: 3-(4-Methylbenzyl)-2,6-di(4-methylphenyl)-
2
H-thiopyran-5-carboxaldehyde (4; C H SO)
28 26
4
-Methylbenzaldehyde (3 g, 0.025 mol) was reacted with sodium sul-
fide (18 g, 0.075) in the presence of aqueous ethanol (1:1, 100 mL)
for 4 h. Column chromatography over silica gel yields [10% benzene
◦
◦
in petroleum ether (60–80 C)] yellow crystals, mp 130 C; yield 2.05 g

3208
A. Banerji et al.
(
60%).; IR: ν = 2916, 2853 (m, CH2−), 1650.5 (s, aldehyde >C=O),
−1
1
206 (s, benzylic), 819.5 (s, 1,4-disubstituted benzene ring); cm ; UV:
1
λmax (log ε) = 368 (3.79) and 266 (4.14) nm; H NMR (CDCl3, δ, 300
MHz): 4.54 (1H, s, H-2), 7.02 (1H, s, H-4), 3.69 and 3.35 (1H, d, J = 15.2,
each, benzylic methylene), 2.39, 2.38, 2.37 (3H, s each, three-CH3), 9.47
(
1H, s, CHO), 7.26 (6H, d, J = 8.0, A,B,C,H-2,6), 7.20 (6H, d, J = 8.0,
13
A,B,C,H-3,5) ppm; C NMR (CDCl3, δ, 75.5 MHz): 46.0 (C-2), 138.1 (C-
3
2
), 119.7 (C-4), 154.6 (C-5), 140.6 (C-6), 42.0 ( CH2-, benzylic), 20.90,
0.91, 21.10 (3-CH3), 186.4 (-CHO), 136.1 (A,C-1), 128.8 (A,C-2,6), 130.9
(
2
A,C-3,5, overlapped signal), 137.7 (A,C-4), 128.5 (B,C-1), 127.2 (B,C-
,6), 130.9 (B,C-3,5, overlapped signal), 137.5 (B,C-4), 131.1 (C,C-1),
30.9 (C,C-2,6, overlapped signal), 128.9 (C,C-3,5), 136.3 (C,C-4) ppm:
1
+
+
+
MS (EI): m/z = 410 (M ), 381 (M −CHO), 319 [M −C6H4CH3], 305
+
•
[
(
M −CH3C6H4CH2], 277 (305—CO), 229 (319—C6H4CH3 + H ), 215
•
+
+
229—CH3C6H4CH2+ H ), 135 [M —C20H18O], 105 [M −C20H17SO],
+
9
1 (C7H7 ). Anal. Calcd. For C28H26SO: C, 82.15; H, 6.40; S, 7.83, Found:
C, 81.95; H, 6.33; S, 7.75.
Reaction of 3-Methylbenzaldehyde (5) with Sodium Sulfide in
Aqueous Ethanol: 3-(3-Methylbenzyl)-2,6-di(3-methylphenyl)-
2
H-thiopyran-5-carboxaldehyle (6; C H SO)
28 26
3
-Methylbenzaldehyde (0.3 g, 0.0025 mol) and sodium sulfide (1.98 g,
.0075 mol) were reacted in aqueous ethanol (1:1, 100 mL) for 6 h. Col-
umn chromatography over silica gel yields [20% benzene in petroleum
0
◦
◦
ether (60–80 C)] yellowish amorphous solid, mp 116 C; yield 0.18 g
53%); IR: ν = 2919.5, 2853.5 (m, CH2-), 1658.5 (s, aldehyde >C=O),
208.5 (s, benzylic), 786.5, 756.5 (s, 1,3-Disubstituted benzene ring);
(
1
−1
1
cm ; UV: λmax (log ε) = 366 (3.09) and 264 (3.48) nm; H NMR (CDCl3,
δ, 300 MHz): 4.50 (1H, s, H-2), 7.00 (1H, s, H-4), 3.66 (1H, d, J = 15,
benzylic), 3.32 (1H, d, J = 15, benzylic), 2.33 (9H, s, 3-CH ), 9.42 (1H, s,
3
CHO), 7.05 (3H, s, A,B,C,H-2), 7.15 (3H, d, J = 4.1, A,B,C,H-4), 7.23
1
3
(
(
3H, br t, A,B,C,H-5), 7.24 (3H, d, J = 5.3, A,B,C,H-6) ppm; C NMR
CDCl3, δ, 125.5 MHz): 46.00 (C-2), 138.6 (C-3), 120.1 (C-4), 155.8 (C-
5
), 141.5 (C-6), 42.9 ( CH2-, benzylic), 21.9, 21.8, 21.6 (3-CH3), 187.2
(-CHO), 138.9 (A,C-1), 131.6 (A,C-2), 134.2 (A,C-3), 128.5 (A,C-4), 126.5
(A,C-5), 129.2 (A,C-6), 128.8 (B,C-1), 130.3 (B,C-2), 133.5 (B,C-3), 128.3
(B,C-4), 124.8 (B,C-5), 128.7 (B,C-6), 138.7 (C,C-1), 132.0 (C,C-2), 132.1
(C,C-3), 128.6 (C,C-4), 127.9 (C,C-5), 129.3 (C,C-6) ppm. Anal. Calcd.
For C28H26SO: C, 82.15; H, 6.40; S, 7.83, Found: C, 82.0; H, 6.30; S,
.70.
7

Synthetic Studies on 2H-Thiopyran Compounds
3209
Reaction of 4-Methoxybenzaldehyde (7) with Sodium Sulfide
in Aqueous Ethanol: 3-(4-Methoxy-benzyl)-2,6-di(4-
methoxyphenyl)-2H-thiopyran-5-carboxaldehyde
(
8; C H SO )
28 26 4
4
-Methoxybenzaldehyde (4.08 g, 0.03 mol) was reacted with sodium
sulfide (21.6 g, 0.09 mol) in aqueous ethanol (1:1, 120 mL) under re-
fluxing conditions for 6 h. Column chromatography [5% benzene in
◦
petroleum ether (60–80 C)] over silica gel yields yellow amorphous
◦
solid (mp 151 C); yield 2.42 g (53%).; IR: ν = 2924.5, 2839.5 (m, −CH2-),
1
651.5 (s, aldehyde >C=O), 1250 (s, C O C group), 829 (s, 1,4-
−1
disubstituted benzene ring); cm ; UV: λmax (log ε) = 361 (3.45), 267
1
(
3.68) and 227 (3.95) nm; H NMR (CDCl3, δ, 300 MHz): 4.55 (1H, s,
H-2), 7.10 (1H, s, H-4), 3.63 (1H, d, J = 15.3, benzylic), 3.30 (1H, d,
J = 15.3, benzylic), 3.78 (9H, s, three-CH ), 9.40 (1H, s, CHO), 7.25
3
(
6H, d, J = 8.5, A,B,C,H-2,6), 6.86 (6H, d, J = 8.5, A,B,C,H-3,5) ppm;
1
3
C NMR (CDCl3, δ, 75.5 MHz): 45.80 (C-2), 133.0 (C-3), 119.6 (C-4),
1
54.5 (C-5), 133.3 (C-6), 64.60 ( CH2-, benzylic), 55.10 (3-OCH3), 186.6
(
-CHO), 130.4 (A,C-1), 128.4 (A,C-2,6, overlapped signal), 114.3 (A,C-
3
1
,5), 159.4 (A,C-4), 126.1 (B,C-1), 128.4 (B,C-2,6, overlapped signal),
13.9 (B,C-3,5), 159.1 (B,C-4), 132.5 (C,C-1), 128.4 (C,C-2,6, overlapped
signal), 114.1 (C,C-3,5), 161.6 (C,C-4) ppm. Anal. Calcd. For C28H26SO4:
C, 73.36; H, 5.67; S, 6.98, Found: C, 73.15; H, 5.50; S, 6.82.
Reaction of 2-Methoxybenzaldehyde (9) with Sodium Sulfide
and Ethanol in Water: 3-(2-Methoxybenzyl)-2,6-di(2-
methoxyphenyl)-2H-thiopyran-5-carboxaldehyde (10;
C H SO )
2
8
26
4
2-Methoxybenzaldehyde (0.68 g, 0.005 mol) and sodium sulfide (3.87
g, 0.015 mol) were reacted in aqueous ethanol (1:1, 20 mL) under re-
fluxing conditions for 6 h. Column chromatography [5% benzene in
◦
petroleum ether (60–80 C)] over silica gel yields afforded the compound
1
◦
0 as yellow amorphous solid, mp 125 C; yield 0.38 g (57%); IR: ν =
2
935, 2837.5 (m, CH2-), 1659 (s, aldehyde >C=O), 1246.5 (s, C O C
−1
group), 751.5 (s, 1,2-disubstituted benzene ring); cm ; UV: λmax (log
1
ε) = 368 (3.26), 262.5 (3.58) and 244.7 (3.64) nm; H NMR (CDCl3, δ,
3
00 MHz): 5.10 (1H, s, H-2), 7.20 (1H, s, H-4), 3.52 (1H, d, J = 15.4,
benzylic), 3.45 (1H, d, J = 15.4, benzylic), 3.72 (9H, s, three-OCH3),
.21 (1H, s, CHO), 6.80–6.90 (9H, m, A,B,C,H-3,4,5), 7.24 (3H, d, J
8.0, A,B,C,H-6) ppm; 13C NMR (CDCl3, δ, 125.5 MHz): 39.65 (C-2),
29.5 (C-3), 120.1 (C-4), 158.0 (C-5), 133.7 (C-6), 37.12 ( CH2-, ben-
zylic), 56.05, 55.86, 55.50 (3-OCH3), 187.8 (-CHO), 128.8 (A,C-1), 156.0
A,C-2), 132.0 (A,C-3), 120.7 (A,C-4), 129.0 (A,C-5), 111.0 (A,C-6), 128.6
9
=
1
(

3210
A. Banerji et al.
(
(
(
B,C-1), 150.0 (B,C-2), 131.0 (B,C-3), 120.3 (B,C-4), 128.2 (B,C-5), 110.6
B,C-6), 131.2 (C,C-1), 157.0 (C,C-2), 134.0 (C,C-3), 120.8 (C,C-4), 131.4
C,C-5), 112.0 (C,C-6) ppm. Anal. Calcd. For C28H26SO4: C, 73.36; H,
5
.67; S, 6.98, Found: C, 73.21; H, 5.56; S, 6.75.
Reaction of Veratraldehyde (11) with Sodium Sulfide in
Aqueous Ethanol: 3-(3,4-Dimethoxybenzyl)-2,6-di(3,4-
dimethoxyphenyl)-2H-thiopyran-5-carboxaldehyde (12;
C H SO )
3
1
32
7
Veratraldehyde (0.83 g, 0.005 mol) was reacted with sodium sulfide
(
3.87 g, 0.015 mol) in aqueous ethanol (1:1, 20 mL) for 7 h. Column chro-
◦
matography [10% benzene in petroleum ether (60–80 C)] over silica gel
yields afforded the pure compound 12 as yellow amorphous solid, mp
◦
1
60 C; yield 0.45 g (50%); IR: ν = 2937.5, 2841.5 (m, CH2-), 1681.5 (s,
−1
aldehyde >C=O), 1269.8 (s, C O C group), cm ; UV: λmax (log ε) =
1
3
38.5 (3.73), and 231.5 (3.93) nm; H NMR (CDCl3, δ, 300 MHz): 4.50
(
1H, s, H-2), 7.00 (1H, s, H-4), 3.66 and 3.53 (1H, d, each, J = 15.4, ben-
zylic), 3.91 (18H, s, 6-OCH3), 9.47 (1H, s, CHO), 7.01 (1H, s, A, H-2),
.70 (1H, d, J = 10.3, A, H-5), 6.90 (1H, d, J = 10.3, A,H-6), 7.25 (1H,
s, B,H-2), 6.60 (1H, d, J = 15.8, B,H-5), 7.50 (1H, d, J = 15.8, B,H-6),
.03 (1H, s, C,H-2), 6.80 (1H, d, J = 8.3, C,H-5), 7.45 (1H, d, J = 8.3,
6
7
1
3
C,H-6) ppm; C NMR (CDCl3, δ, 125.5 MHz): 46.50 (C-2), 144.5 (C-3),
20.0 (C-4), 155.7 (C-5), 143.9 (C-6), 42.40 ( CH2-, benzylic), 56.30 (6-
OCH3), 187.1 (-CHO), 127.7 (A,C-1), 125.1 (A,C-2), 132.4 (A,C-3), 149.4
1
(
(
(
A,C-4), 112.6 (A,C-5), 120.4 (A,C-6), 126.6 (B,C-1), 123.4 (B,C-2), 131.2
B,C-3), 149.3 (B,C-4), 111.6 (B,C-5), 120.2 (B,C-6), 128.7 (C,C-1), 125.6
C,C-2), 133.5 (C,C-3), 151.7 (C,C-4), 114.4 (C,C-5), 121.5 (C,C-6) ppm.
Anal. Calcd. For C31H32SO7: C, 67.75; H, 6.01; S, 5.82, Found: C, 67.62;
H, 5.85; S, 5.70.
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3211
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