Studies in sulfur heterocycles. Part 16:1,2 synthesis of [1]benzothieno[3,2-b]pyrans via tandem reactions from 2,3-dihydrobenzo[b]thiophene-3(2H)ones

Article abstract of DOI:10.1055/s-2003-40825

Sequential treatment of N,N-diethyl-2-methylsulfanyl aryl amides with LDA and p-anisaldehyde, 1-naphthaldehyde and cinnamaldehyde afforded the corresponding thioaurones. Heating the thioaurones derived from cinnamaldehyde, above 200°C resulted in electrocyclic ring closure and sigmatropic shift in tandem to give substituted [1]benzothieno[3,2-b]pyran. Treatment of N,N-diethyl-2-methylsulfanyl-5-methoxy benzamide and crotonaldehyde gave 4-methyl-8-methoxy[1]benzothieno[3,2-b]pyran via conjugate nucleophilic addition and ring closure in one pot. Possible mechanistic pathways are discussed.

Full text of DOI:10.1055/s-2003-40825

LETTER
1479
Studies in Sulfur Heterocycles. Part 16:1,2 Synthesis of [1]Benzo-
thieno[3,2-b]pyrans via Tandem Reactions from 2,3-Dihydrobenzo[b]thio-
phene-3(2H)ones
Synthesisof [1
u
]Benzothien
k
o[3,2-
b
]
pyra
a
ns nta Kamila, Chandrani Mukherjee, Asish De*
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata-700032, W.B, India
E-mail: ocad@mahendra.iacs.res.in
Received 6 May 2003
the basis of spectroscopic and analytical data, the result-
ing compounds were assigned the structures 2-phenyl-6-
methoxy[1]benzothieno[3,2-b]pyran (6) and 2-phenyl-8-
methoxy[1]benzothieno[3,2-b]pyran (7) respectively.8
Abstract: Sequential treatment of N,N-diethyl-2-methylsulfanyl
aryl amides with LDA and p-anisaldehyde, 1-naphthaldehyde and
cinnamaldehyde afforded the corresponding thioaurones. Heating
the thioaurones derived from cinnamaldehyde, above 200 °C result-
ed in electrocyclic ring closure and sigmatropic shift in tandem to
give substituted [1]benzothieno[3,2-b]pyran. Treatment of N,N-di-
ethyl-2-methylsulfanyl-5-methoxy benzamide and crotonaldehyde
gave 4-methyl-8-methoxy[1]benzothieno[3,2-b]pyran via conju-
gate nucleophilic addition and ring closure in one pot. Possible
mechanistic pathways are discussed.
It is interesting to note that the signal due to C-2 in each
case appears at d = 186.8 ppm. This considerable down-
field shift is explained by its attachment to the ring oxygen
atom, phenyl ring and the double bond. On the other hand
the signal due to C-3 appears at d = 83.3 and 83.4 ppm for
compounds 6 and 7. This upfield shift is accounted for by
substitution pattern. COSY and HMBC spectra estab-
lished the assignments beyond doubt (Figure 1).
Key words: thioaurones, electrocyclic ring closure, sigmatropic
shift, benzothiopyran
Recently we reported3,4 the synthesis of substituted thioin-
doxyls, key intermediates in the synthesis of diversely
substituted benzo[b]thiophenes, through side-chain
deprotonation and instantaneous intramolecular nucleo-
philic attack on the carbonyl carbon by the incipient an-
ion. After the publication of our initial results,3 Cabiddu5
reported the formation of thioindoxyls from commercially
available ethyl-2-methyl sulfanyl benzoates, following
the same principle and the conversion of the thioindoxyls
into their 2-arylmethylidene or 2-alkylmethylidene deriv-
atives, commonly known as thioaurones. This prompts us
to report our initial findings in this area.
Resurgence of interest in thioaurones,6 in recent times is
due to their manifold uses.5 We developed a one-pot syn-
thesis of thioaurones from N,N-diethyl-2-methylsulfanyl
aryl amides as shown in Table 1.7 When compounds 1 and
2 were heated in a silicone oil bath at 210 °C (bath tem-
perature) for 7 hours, a brown mass was obtained in each
case which, on chromatography over silica gel, afforded
colourless crystalline compounds [eluant: EtOAc:light
petroleum (3:17)]. The carbonyl peaks were absent in the
IR spectra. In the proton NMR spectra apart from the
methoxy signals, a two proton multiplet was present for
both the compounds at d = 2.88 to 3.22 ppm. The aromatic
region showed the presence of a six proton multiplet and
three doublet of doublets. In the 13C NMR there were sig-
nals due to six quaternary carbons of which three are con-
siderable down field. Signals due to methyl and
methylene carbons were present in appropriate places. On
Figure 1
Formation of these two tricyclic compounds is accounted
for by a plausible mechanistic pathway shown in
Scheme 1. The pathway consists of electrocyclic ring clo-
sure (of cisoid conformation) and [1,3]hydrogen shift in
tandem. Severe geometrical constraints associated with
antarafacial shift suggests the possibility of an alternative
two stage mechanism, the exact nature of which is under
investigation.
When N,N-diethyl-2-methylsulfanyl-5-methoxy benza-
mide was treated sequentially with LDA and crotonalde-
hyde, a gummy product was obtained which upon
repeated chromatography afforded a thick liquid which
did not show any absorption due to a carbonyl group in the
IR spectrum. 1H NMR spectrum showed two three proton
signals at d = 3.89 and 1.61 ppm as singlet and doublet re-
spectively. On the basis of analytical and spectral data,
this compound is assigned the structure 4-methyl-8-meth-
oxy[1]benzothieno[3,2-b]pyran (8) which is formed via
three reactions taking place in tandem viz. formation of
thioindoxyl, conjugate nucleophilic addition and ring clo-
sure as shown in Scheme 2.
Synlett 2003, No. 10, Print: 05 08 2003.
Art Id.1437-2096,E;2003,0,10,1479,1481,ftx,en;D10203ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
We have reported above a new approach towards the
synthesis of benzothieno[3,2-b]pyran. These compounds

1480
S. Kamila et al.
LETTER
Table 1 One-Pot Synthesis of Thioaurones from N,N-Diethyl-2-methylsulfanyl Aryl Amides
Entry
1
Compounds
Yield (%)
83
2
3
74
84
4
5
78
69
belong to a system of which there are only few reports and
Acknowledgement
their formation in one pot reaction is particularly conve-
nient. Work is in progress for synthesising more com-
pounds of this class and more in depth study of the
mechanisms.
A. D. thanks Royal Society of Chemistry for financial assistance. S.
K. thanks Council of Scientific and Industrial Research (New De-
lhi) for Senior Research Fellowship under project no. 01(1573)/99/
EMR-II. Thanks are due to Professor R. W. Alder for helpful dis-
cussion.
Scheme 1
Synlett 2003, No. 10, 1479–1481 © Thieme Stuttgart · New York

LETTER
Synthesis of [1]Benzo-thieno[3,2-b]pyrans
1481
Scheme 2
References
Compound 2: Yellowish solid, yield 74%, mp 146–147 °C.
IR (KBr): 1639.4 cm–1. 1 H NMR (300 MHz, CDCl3): d =
7.80 (d, 1 H, J = 15.5 Hz), 7.59–7.55 (m, 2 H), 7.52 (s, 1 H),
7.37–7.35 (m, 3 H), 7.30 (d, 1 H, J = 2.4 Hz), 7.12 (dd, 1 H,
J = 2.4, 8.8 Hz), 6.95 (d, 1 H, J = 15.5 Hz). 13 C NMR (75
MHz, CDCl3): d = 186.3, 164.4, 158.1, 144.6, 134.8, 132.7,
131.8, 131.3, 129.4-129.1, 124.5,122.8, 122.1, 56.0. Anal.
Calcd for C18H14O2S: C, 73.40; H, 4.76. Found: C, 73.10; H,
4.60.
(1) Part 15, see: Ghosh, S. C.; De, A. J. Chem. Soc., Perkin
Trans. 1 1999, 2639.
(2) Abstracted in part from the PhD thesis of S. K submitted to
Jadavpur University (2003).
(3) Mukherjee, C.; De, A. Synlett 2002, 325.
(4) Mukherjee, C.; Kamila, S.; De, A. Tetrahedron 2003 (in
press).
(5) Cabiddu, M. G.; Cabiddu, S.; Cabiddu, E.; de Montis, S.;
Fattuoni, C.; Melis, S.; Usai, M. Synthesis 2002, 875.
(6) (a) Perold, G. W.; van Ligen, P. F. A. Chem. Ber. 1959, 92,
253. (b) Guha, S. K.; Chatterjea, J. N.; Mishra, A. K. Chem.
Ber. 1961, 94, 3297. (c) Cagniant, P.; Kirsch, G.; Cagniant,
D. C. R. Acad. Sci. Ser. C 1972, 74. (d) Hofman, H.;
Westernacher, H.; Haberstroh, H. J. Chem. Ber. 1973, 106,
349. (e) Wadsworth, D. H.; Detty, M. R. J. Org. Chem.
1980, 45, 4611. (f) Taylor, A. W.; Dean, D. K. Tetrahedron
Lett. 1988, 29, 1845.
Compound 6: Colourless needle shaped crystal, yield 78%,
mp 194–195 °C. 1 H NMR (300 MHz, CDCl3): d = 7.55–7.42
(m, 6 H), 7.35 (dd, 1 H, J = 7.8, 8.5 Hz), 6.93 (dd, 1 H, J =
7.8 Hz), 5.70 (dd, 1 H, J = 3.3, 3.4 Hz), 4.00 (s, 3 H), 3.22–
2.88 (m, 2 H). 13 C NMR (75 MHz, CDCl3): d = 186.8, 161.5,
155.1, 138.4, 132.0, 130.7, 129.4, 129.3, 126.7, 126.6,
116.1, 115.8, 109.1, 83.2, 56.2, 44.4. Anal. Calcd for
C18H14O2S: C, 73.40; H, 4.76. Found: C, 73.50; H, 4.80.
Compound 7: Colourless solid, yield 65%, mp 207 °C. 1
H
NMR (300 MHz, CDCl3): d = 7.50 (d, 1 H, J = 8.8 Hz), 7.50–
7.22 (m, 6 H), 7.10 (dd, 1 H, J = 2.5, 8.8 Hz), 5.67 (dd, 1 H,
J = 3.2, 3.3 Hz), 3.78 (s, 3 H), 3.18–2.80 (m, 2 H). 13 C NMR
(75 MHz, CDCl3): d = 186.7, 158.1, 138.3, 134.0, 131.8,
129.5, 129.4, 129.3, 129.3, 126.9, 124.9, 121.3, 104.0, 83.4,
56.0, 44.4. Anal. Calcd for C18H14O2S: C, 73.40; H, 4.76.
Found: C, 73.50; H, 4.80.
(7) Representative Experimental Procedure for the
Preparation of the Thioaurones:
N,N-Diethyl-2-methylsulfanyl aryl amides were treated with
LDA at 0 °C under argon and after a brief interval, the
aldehyde was added by syringe. The temperature was kept at
0 °C for 1 h under inert atmosphere. Usual acidic work up
after this period afforded the thioaurones in very good
yields.
Compound 1: Yellowish fluffy solid, yield 83%, mp 152–
153 °C. IR (KBr): 1635 cm–1. 1 H NMR (300 MHz, CDCl3):
d = 7.93 (d, 1 H, J = 15.4 Hz), 7.67–7.64 (m, 2 H), 7.61 (s, 1
H), 7.45–7.41(m, 3 H), 7.38 (dd, 1 H, J = 7.9, 8.1 Hz), 7.10
(d, 1 H, J = 15.4 Hz), 6.97 (dd, 1 H, J = 7.9 Hz), 4.02 (s, 3
H). 13 C NMR (75 MHz, CDCl3): d = 186.4, 165.2, 154.8,
144.6, 134.8, 133.0, 132.6, 131.3, 129.4-129.1, 126.6, 122.9,
116.4, 109.5, 53.6. Anal. Calcd for C18H14O2S: C, 73.40; H,
4.76. Found: C, 73.48; H, 4.74.
(8) Compound 8: Prepared in the same way as before except
crotonaldehyde was used instead of aromatic aldehyde.
Yellowish gummy liquid, yield 40%. 1 H NMR (300 MHz,
CDCl3): d = 7.75 (dd, 2 H, J = 8.9 Hz), 7.19 (dd, 1 H, J = 2.1
Hz), 6.99 (dd, 1 H, J = 2.1, 8.8 Hz), 4.88–4.84 (m, 1 H), 3.89
(s, 3 H), 2.80–2.60 (m, 1 H), 1.61 (d, 3 H). 13 C NMR (75
MHz, CDCl3): d = 154.6, 140.2, 134.7, 133.8, 132.1, 125.7,
124.5, 122.5, 111.9, 108.9, 5, 29, 2. Anal. Calcd for
C18H12O2S: C, 67.24; H, 5.17. Found: C, 67.30; H, 5.40.
Synlett 2003, No. 10, 1479–1481 © Thieme Stuttgart · New York