T. A. Dias, M. F. Proença / Tetrahedron Letters 53 (2012) 5235–5237
5237
Previous studies by O’Callaghan et al.16 on the NMR spectra of
unsubstituted 2-imino-2H-chromene-3-carboxamides revealed
that the spectra of these compounds in DMSO-d6, showed the pres-
ence of a mixture of both 2-imino-2H-chromene-3-carboxamide
and the isomeric 2-cyano-3-(2-hydroxyphenyl)-prop-2-enamide.
The authors also concluded that the nature and position of the sub-
stituents on C-6 and/or C-8 of the chromene scaffold affected the
extent of isomerization. The use of other deuterated solvents led
to a single isomer in solution, identified as the cyclic 2-imino-
chromene.
3. Kempen, I.; Hemmer, M.; Counerotte, S.; Pochet, L.; Tullio, P.; Foidart, J.;
Blacher, S.; Noel, A.; Frankenne, F.; Pirotte, B. Eur. J. Med. Chem. 2008, 43, 2735–
2750.
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Bioorg. Med. Chem. Lett. 2010, 20, 3889–3892.
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Bioorg. Med. Chem. Lett. 2012, 22, 4807–4809.
7. Chimenti, F.; Bizzarri, B.; Bolasco, A.; Secci, D.; Chimenti, P.; Carradori, S.;
Arianna, G.; Rivanera, D.; Lilli, D.; Zicari, A.; Scaltritod, M.; Sisto, F. Bioorg. Med.
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295.
A similar study was performed for 3-phenylsulfonyl-2-imino-
chromene 4b comprising different deuterated solvents namely
chloroform-d3, methanol-d4, acetone-d6 and acetonitrile-d3. The
spectra were recorded at 20 °C, using 5 mg of product in 650 lL
11. Heffernan, G.; Coghlan, R.; Manas, E.; McDevitt, R.; Li, Y.; Mahaney, P.;
Robichaud, A.; Huselton, C.; Alfinito, P.; Bray, J.; Cosmi, S.; Johnston, G.; Kenney,
T.; Koury, E.; Winneker, R.; Deecher, D.; Trybulski, E. Bioorg. Med. Chem. 2009,
17, 7802–7815.
12. Ivachtchenko, A.; Golovina, E.; Kadieva, M.; Koryakova, A.; Kovalenko, S.;
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Chem. 2010, 18, 5282–5290.
of solvent. Under these conditions, a reduced extent of isomeriza-
tion was observed, as was summarized in Table 3. The intensity of
the protons on C-4 (for 4b) and on C-3 (for 3b) was used to calcu-
late the degree of isomerization in each solvent.
The 3-phenyl-sulfonyl-2H-chromen-2-ones 5a–g were obtained
from the hydrolysis of the corresponding compounds 4a–g, in
aqueous HCl. The solution was kept in a water bath at 80° for
1.5–3.5 h and the pure product precipitated from the reaction
medium requiring no further purification (Table 4).17
In conclusion, a simple and ecofriendly method was developed
for the synthesis of 2-imino- and 2-oxo-3-phenylsulfonyl-2H-
chromenes, isolated in excellent yield. Most of these compounds
are new chromene derivatives, analogous to bioactive molecules.
They may also be considered useful precursors for a number of
chromene-based structures as the phenylsulfonyl substituent can
13. El-Shafei, A.; Fadda, A.; Abdel-Gawad, I.; Youssif, E. Synth. Commun. 2009, 39,
2954–2972.
14. Proença, F.; Costa, M. Green Chem. 2008, 10, 995–998.
15. (a) General procedure for the synthesis of 3-(phenylsulfonyl)-2H-chromen-2-
imines 4 (for details see Table 2): A suspension of (phenylsulfonyl)acetonitrile 1
and aromatic aldehyde 2 in a 0.05 M sodium carbonate solution, was stirred at
room temperature, until the starting material was totally consumed, as
evidenced by TLC. The solid formed was filtered and washed with distilled
water. (b) Analytical and spectroscopic data for a representative compound, 8-
methoxy-3-(phenylsulfonyl)-2H-chromen-2-imine (4b): Mp 202–205 °C. IR
(Nujol mull):
m 3306, 1671, 1641, 1605, 1569, 1374, 1320, 1274, 1213, 1158,
1086 cmÀ1 1H NMR (400 MHz, DMSO-d6): d 3.83 (s, 3H, 4), 3.84 (s, 3H, 3), 6.86
.
(t, 1H, J = 8.4 Hz, 3), 7.19 (dd, 1H, J = 8.4, 1.2 Hz, 3), 7.20 (t, 1H, J = 7.0 Hz, 4),
7.28 (d, 1H, J = 7.2 Hz, 4), 7.39 (d, 1H, J = 7.2 Hz, 4), 7.53 (dd, 1H, J = 8.4, 1.2 Hz,
3), 7.60 (t, 1H, J = 6.8 Hz, 4), 7.71 (t, 2H, J = 7.6 Hz, 3) 7.73 (d, 2H, J = 6.8 Hz, 4),
7.82 (dt, 1H, J = 7.6, 2.0 Hz, 3), 7.96 (t, 2H, J = 7.6 Hz, 3), 7.98 (t, 2H, J = 6.8 Hz, 4),
8.56 (s, 1H, 4), 8.72 (s, 1H, 3), 8.89 (s, 1H, 4), 10.26 (s, 1H, 3) ppm. 13C NMR
(100 MHz, DMSO-d6): d 56.01 (3), 56.10 (4), 109.99 (3), 113.76 (3), 116.76 (4),
117.09 (3), 117.12 (3), 117.80 (4), 118.72 (3), 119.14 (3), 121.98 (4), 123.92 (4),
127.89 (2C, 4), 128.73 (2C, 3), 128.78 (2C, 4), 129.02 (4), 130.12 (2C, 3), 133.71
(4), 134.86 (3), 137.97 (3),139.10 (4), 142.49 (4), 143.86 (4), 145.88 (4), 146.76
be used as
substitution.
a convenient leaving group for nucleophilic
Acknowledgments
We gratefully acknowledge the financial support by the Univer-
sity of Minho and the Foundation for Science and Technology (FCT),
Portugal, through the National NMR Network (Bruker 400 Avance
III) and also the research grants PEst-C/QUI/UI0686/2011 and
PEst-C/BIA/UI4050/2011, that are co-funded by the program COM-
PETE from QREN with co-participation from the European Commu-
nity fund FEDER.
(3), 148.21 (4), 148.64 (3), 150.37 (3) ppm. Anal. Calcd. for
C16H13NO4S
(315.06): C, 60.94; H, 4.16; N, 4.44; S, 10.17. Found C, 61.03; H, 4.30; N, 4.65; S,
10.42.
16. O’Callaghan, C.; McMurry, T.; O’ Brien, J. J. Chem. Soc., Perkin Trans. 2 1998, 425–
429.
17. (a) General procedure for the synthesis of 3-(phenylsulfonyl)-2H-chromen-2-
ones 5 (for details see Table 4): Concentrated HCl (37%) was added to a
suspension of 3-(phenylsulfonyl)-2H-chromen-2-imine 4 in distilled water. The
mixture was stirred in a water bath, at 80 °C, until the full consumption of
starting material was evidenced by TLC. The solid formed was filtered and
washed with distilled water. All the isolated compounds were fully
characterized from their physical, analytical, and spectroscopic data. (b)
Analytical and spectroscopic data for a representative compound, 8-methoxy-
Supplementary data
Supplementary data associated with this article can be found, in
069. These data include MOL files and InChiKeys of the most
important compounds described in this article.
3-(phenylsulfonyl)-2H-chromen-2-one (5b): Mp 268–270 °C. IR (Nujol mull):
m
1721, 1607, 1571, 1362, 1329, 1306, 1161, 1137 cmÀ1 1H NMR (300 MHz,
.
60 °C, DMSO-d6): d 3.96 (s, 3H), 7.39 (t, 1H, J = 8.1 Hz), 7.47 (dd, 1H, J = 8.1,
1.5 Hz), 7.60 (dd, 1H, J = 8.1, 1.5 Hz), 7.64 (dt, 2H, J = 7.5, 1.5 Hz), 7.73 (dt, 1H,
J = 7.5, 1.5 Hz), 8.01 (dd, 2H, J = 7.5, 1.5 Hz), 9.06 (s, 1H) ppm. 13C NMR
(75 MHz, 60 °C, DMSO-d6): d 56.25, 117.66, 117.79, 122.00, 125.01, 126.76,
128.18, 128.92, 133.81, 138.50, 144.25, 146.25, 148.93, 154.03 ppm. Anal.
Calcd for C16H12O5S (316.04): C, 60.75; H, 3.82; S, 10.14. Found C, 60.63; H,
3.58; S, 9.97.
References and notes
1. Proença, F.; Costa, M. Tetrahedron 2010, 66, 4542–4550.
2. Fadda, A.; Refat, H.; Zaki, M. Molecules 2000, 5, 701–709.