G. Mugesh and B. K. Sarma
Synthesis of 10: Glutathione (GSH) (112 mg, 0.36 mmol) in water (2 mL)
was added to a stirred solution of ebselen (0.1 g, 0.36 mmol) in MeOH
(2 mL). The reaction mixture was stirred for 0.5 h at ambient tempera-
ture. The precipitate formed was filtered, washed repeatedly with water
and CH2Cl2, and dried in vacuo to give 10 as a white solid in 70% yield.
77Se NMR (CDCl3): d=545 ppm; elemental analysis calcd (%) for
C23H26N4O7SSe: C 47.51, H 4.51, N 9.63; found: C 45.53, H 3.91, N 9.52.
(SIR-92) and refined by the full-matrix least-squares procedure on F2 for
all reflections (SHELXL-97).[61]
Crystal data for 6: C26H20N2O2Se2; Mr =550.4; monoclinic; space group
C2/c; a=24.4233, b=5.0510(21), c=19.2476(79) ꢁ; b=109.618(6)8; V=
2236.59(53) ꢁ3; Z=4, 1calcd =1.63 gcmꢀ1; MoKa radiation (l=0.71073 ꢁ);
T=291(2) K; R1 =0.031, wR2 =0.068 (I>2s(I)); R1 =0.044, wR2 =0.072
(all data).
Synthesis of 14: Benzenethiol (230 mL, 2.24 mmol) was added to a stirred
solution of 17 (0.6 g, 2.22 mmol) in CH2Cl2 (10 mL). The reaction mixture
was stirred for 24 h at ambient temperature. The solvent was then re-
moved in vacuo and 14 was then purified by flash chromatography by
using petroleum ether/ethyl acetate as the eluent to give 14 as a colorless
oil in 60% yield. 1H NMR (CDCl3): d=8.15 (d, J=8.0 Hz, 1H), 7.50 (d,
J=7.6 Hz, 3H), 7.43 (t, J=7.6 Hz, 3H), 7.21–7.28 (m, 3H), 7.15 (t, J=
6.8, 7.2 Hz, 1H), 6.36 (s, 1H), 3.73 (s, 2H), 1.44 ppm (s, 6H); 13C NMR
(CDCl3): d=168.4, 136.8, 136.6, 132.1, 131.5, 128.9, 126.6, 126.4, 126.0,
70.1, 56.5, 24.5 ppm; 77Se NMR (CDCl3): d=585 ppm; HRMS (TOF MS
ES+): m/z: 404.0200 [M+Na]+.
Crystal data for 9: C13H11NO3Se; Mr =308.2; orthorhombic; space group
Pna2(1);
a=19.0020(39),
b=14.1292(29),
c=4.5882(9) ꢁ;
V=
1231.85(4) ꢁ3; Z=4; 1calcd =1.66 gcmꢀ1; MoKa radiation (l=0.71073 ꢁ);
T=291(2) K; R1 =0.037, wR2 =0.065 (I>2s(I)); R1 =0.059, wR2 =0.071
(all data).
Crystal data for 16: C22H28N2O4Se2; Mr =542.4; monoclinic; space group
P2(1)/n; a=8.4090(50), b=15.3440(50), c=18.1000(50) ꢁ; b=95.268(5)8;
V=2325.54(20) ꢁ3; Z=4; 1calcd =1.55 gcmꢀ1
;
MoKa radiation (l=
0.71073 ꢁ); T=291(2) K; R1 =0.060, wR2 =0.118 (I>2s(I)); R1 =0.126,
wR2 =0.142 (all data).
Crystal data for 19: C14H13NO2Se; Mr =306.2; monoclinic; space group
P2(1)/C; a=9.5949(12), b=7.2494(9), c=19.7972(24) ꢁ; b=98.011(2)8;
Synthesis of 16: Excess benzenethiol (1 mL, 9.7 mmol) was added to a
stirred solution of 17 (0.6 g, 2.22 mmol) in CH2Cl2 (10 mL). The reaction
mixture was stirred for 48 h at ambient temperature and the reaction
mixture was kept for aerial oxidation for another 48 h. The solvent was
then removed in vacuo and the diselenide was purified by column chro-
matography by using petroleum ether/ethyl acetate 1:1 as the eluent to
give 16 as a yellow solid in 60% yield. 1H NMR ([D4]MeOH): d=7.84
(d, J=7.6 Hz, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.26–7.35 (m, 2H), 3.75 (s,
2H), 1.46 ppm (s, 6H); 13C NMR ([D4]MeOH): d=168.4, 134.3, 130.0,
129.7, 126.2, 124.9, 66.7, 54.5, 21.57 ppm; 77Se NMR ([D4]MeOH): d=
429 ppm; HRMS (TOF MS ES+): m/z: 567.0295 [M+Na]+.
V=1363.60(5).16) ꢁ3; Z=4; 1calcd =1.49 gcmꢀ1
; MoKa radiation (l=
0.71073 ꢁ); T=291(2) K; R1 =0.032, wR2 =0.077 (I>2s(I)); R1 =0.046,
wR2 =0.083 (all data).
Acknowledgements
This study was supported by the Department of Science and Technology
(DST), New Delhi (India). We also thank the DST for the CCD single-
crystal X-ray diffraction facility. We are grateful to the Alexander von
Humboldt Foundation, Bonn, Germany for the donation of an automated
flash chromatography system. We express appreciation to Dr. P.P. Phad-
nis for his help in performing some of the 77Se NMR experiments and
Dr. M. Nethaji for his help in solving the X-ray structures. G.M. acknowl-
edges the DST for the award of a Ramanna fellowship.
Synthesis of 17: 2-(Chloroseleno)benzoyl chloride (1.23 g, 4.83 mmol) in
acetonitrile (15 mL) was added dropwise to a stirred solution of 2-amino-
2-methylpropan-1-ol (480 mL, 5 mmol) in dry acetonitrile (50 mL). The
reaction mixture was stirred for 5 h at 258C and then the precipitate
formed was filtered off. The filtrate was evaporated under reduced pres-
sure to give a colorless oil, which was then purified by column chroma-
tography by using petroleum ether/ethyl acetate 5:1 as the eluent to give
17 as a white solid in 80% yield. 1H NMR (CDCl3): d=7.89 (d, J=
8.0 Hz, 1H), 7.52 (d, J=3.2 Hz, 2H), 7.34–7.37 (m, 1H), 5.50 (brs, 1H),
3.85 (s, 2H), 1.52 ppm (s, 6H); 13C NMR (CDCl3): d=167.0, 137.0, 131.0,
128.1, 127.6, 125.2, 122.2, 69.2, 62.9, 24.9 ppm; 77Se NMR (CDCl3): d=
885 ppm; HRMS (TOF MS ES+): m/z: 294.0032 [M+Na]+.
313–323; e) T. Schewe, Gen. Pharmacol. 1995, 26, 1153–1169;
7332, and references therein. g) H. Sies, H. Masumoto, Adv. Phar-
macol. 1997, 38, 229–246; h) G. Mugesh, H. B. Singh, Chem. Soc.
Rocha, Chem. Rev. 2004, 104, 6255–6286.
[2] H. Masumoto, R. Kissner, W. H. Koppenol, H. Sies, FEBS Lett.
1996, 398, 179–182.
[3] N. Noguchi, Y. Yoshida, H. Kaneda, Y. Yamamoto, E. Niki, Bio-
[4] A. Zembowicz, R. J. Hatchett, W. Radziszewski, R. J. Gryglewski, J.
Pharmacol. Exp. Ther. 1993, 267, 1112–1118.
[5] R. Hattori, R. Inoue, K. Sase, H. Eizawa, K. Kosuga, T. Aoyama, H.
Masayasu, C. Kawai, S. Sasayama, Y. Yui, Eur. J. Pharmacol. 1994,
267, R1–R2.
Computational methods: All calculations were performed by using the
Gaussian 98 suite of quantum chemical programs.[53] The hybrid Becke 3-
Lee-Yang-Parr (B3LYP) exchange correlation functional was applied for
DFT calculations.[47] Geometries were fully optimized at the B3LYP level
of theory by using the 6-31G(d) basis sets. Transition states were located
by using Schlegelꢃs synchronous transit-guided quasi-Newton (STQN)
method.[54, 55] Transition states were searched by using the QST3 keyword
and the resultant conformation was optimized by using the TS keyword.
Furthermore, the transition state and the stable conformers were charac-
terized by the presence or absence of a single imaginary mode. In all
cases, intrinsic reaction coordinate (IRC)[56] calculations were performed
to confirm that the transition states connect the reactant and the product
molecules. The activation energies are the difference in the zero-point vi-
brational energy corrected electronic energy between the transition state
and the stable conformations. Orbital interactions were analyzed by
using the NBO method at the B3LYP/6-31G(d) level.[48]
X-ray crystallography: X-ray crystallographic studies were carried out on
a Bruker CCD diffractometer with graphite-monochromatized MoKa ra-
diation (l=0.71073 ꢁ) controlled by a Pentium-based PC running on the
SMART software package.[57] Single crystals were mounted at room tem-
perature on the ends of glass fibers and data were collected at room tem-
perature. The structures were solved by direct methods and refined by
using the SHELXTL software package.[58] All non-hydrogen atoms were
refined anisotropically and hydrogen atoms were assigned idealized loca-
tions. Empirical absorption corrections were applied to all structures by
using SADABS.[59–60] The structures were solved by the direct method
65–74; b) V. Galet, J.-L. Bernier, J.-P. Hꢂnichart, D. Lesieur, C.
Abadie, L. Rochette, A. Lindenbaum, J. Chalas, J.-F. Renaud de la
[7] I. A. Cotgreave, S. K. Duddy, G. E. N. Kass, D. Thompson, P. Mol-
10612
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 10603 – 10614