First synthesis of 1,3-oxaselenepanes

Article abstract of DOI:10.1016/j.tetlet.2009.04.004

The first synthesis of 1,3-oxaselenepane derivatives by the reaction of aryl isoselenocyanates with 4-bromobutanol in the presence of sodium hydride in THF as a one-pot reaction is described. The Z/E isomerism for the exocyclic carbon-nitrogen double bond

Full text of DOI:10.1016/j.tetlet.2009.04.004

Tetrahedron Letters 50 (2009) 3035–3037
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First synthesis of 1,3-oxaselenepanes
Dinesh R. Garud a, Yosuke Toyoda a, Mamoru Koketsu b,
*
a Department of Chemistry, Faculty of Engineering, Gifu University, Gifu 501-1193, Japan
b Department of Material Science and Technology, Faculty of Engineering, Gifu University, Gifu 501-1193, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The first synthesis of 1,3-oxaselenepane derivatives by the reaction of aryl isoselenocyanates with
4-bromobutanol in the presence of sodium hydride in THF as a one-pot reaction is described. The Z/E
isomerism for the exocyclic carbon–nitrogen double bond in the selenium heterocycles was observed
for the first time.
Received 4 March 2009
Revised 27 March 2009
Accepted 2 April 2009
Available online 7 April 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Selenium
Isoselenocyanate
1,3-Oxaselenepanes
In recent years, interest in synthesis of selenium-containing
compounds has increased because of their interesting reactivities1
and their potential biological activity. The biological and medicinal
properties of selenium and organoselenium compounds are
increasingly appreciated, mainly due to their antioxidant, antitu-
mor, antimicrobial, and antiviral properties.2 The selenoureas3
and selenoamides3a,4 have been extensively studied for the synthe-
sis of selenium-containing heterocycles. In this context, isoseleno-
cyanates5 have been emerged as a powerful tool for the synthesis
of selenium-containing heterocycles, since they are easy to prepare
and store and are safe to handle. Our group has shown the utility of
isoselenocyanates in the synthesis of a variety of four-,6 five-,7 or
six-membered8 selenium-containing heterocycles.
excess of triphosgene, selenium, and triethylamine according to
the previous literature.10 First, the reaction of phenyl isoselenocy-
anate 1a with 4-bromobutanol using 2.5 equiv of NaH was exam-
ined in CH2Cl2 at 0 °C to rt and the cyclized product 2a was
obtained only in traces after work-up of the reaction mixture. To
improve the yield of the reaction, different conditions were then
screened. Finally, 1.5 equiv of 4-bromobutanol and 1.8 equiv of
NaH were suitable for the cyclization reaction, furthermore the
reaction was influenced by the solvent used and the best result
was obtained when the reaction was carried out in THF (29%, entry
1, Table 1) (Scheme 1).11 The use of 4-chlorobutanol in the present
reaction leads to the formation of required 1,3-oxaselenepanes 2a
in traces.12
In contrast, only a few examples for the synthesis of seven-
membered selenium-containing heterocycles, such as 1,3-sele-
nazepines, have been reported in the literature.9 For example,
our group has reported the synthesis of b-lactam-fused 1,3-sele-
nazepines,9a,b whereas the Russian team has published an article
concerning the synthesis of 1,3-selenazepane fused with a pyri-
midinone system.9c Heimgartner et al. reported the synthesis of
1,3-selenazepanes by the reaction of isoselenocyanates with
5-chlorobutylamine.9d However, it is surprising to note that there
is no report on the synthesis of seven-membered selenium-con-
taining heterocycles such as 1,3-oxaselenepanes. Herein we report
for the first time, the synthesis of 1,3-oxaselenepanes by the reac-
tion of isoselenocyanates with 4-bromobutanol and its Z and
E isomerism.
The compound 2a was isolated as an inseparable mixture of Z
and E isomers (6.9:1 ratio) at the imine position. The structure of
2a was elucidated by studies of IR, 1H, 13C, 77Se NMR, COSY, HMQC,
HMBC and NOESY, MS, elemental analysis, and X-ray analysis. All
attempts to separate the Z and E isomers were failed. In the 77Se
NMR spectra of the 1,3-oxaselenepane 2a, two 77Se signals were
observed d 361.4 for the Z isomer and d 383.3 for E isomer which
were at a higher field as compared with 77Se signals of selenocar-
bonyl compounds (d 1420–2131).13 The values are typical for a C–
Se single bond with an sp3 selenium atom and not for a C@Se
double bond with an sp2 selenium atom.14 Under similar reaction
conditions, the reactions of six isoselenocyanates 1 with 4-bromo-
butanol gave the 2-imino-1,3-oxaselenopanes 2 as mixture of Z
and E isomers in 4–32% yields (Table 1). Aryl isoselenocyanates
1a–d provided the corresponding 1,3-oxaselenepanes 2a–d in
moderated yields (entries 1–4). The benzyl isoselenocyanate 1e
afforded the 1,3-oxaselenepanes 2e in 23% yield (entry 5). The
use of cyclohexyl isoselenocyanate 1f in the reaction was found
to be difficult and the cyclized product 1,3-oxaselenepanes 2e
For our approach substituted alkyl and aryl isoselenocyanates 1
were prepared by reactions of N-substituted formamides with an
* Corresponding author. Tel./fax: +81 58 293 2619.
E-mail address: koketsu@gifu-u.ac.jp (M. Koketsu).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.04.004

3036
D. R. Garud et al. / Tetrahedron Letters 50 (2009) 3035–3037
Table 1
Synthesis of 1,3-oxaselenepanes 2
Entry
1
Isoselenocyanate
Product
Yielda (%)
29
Ratio (Z/E)b
N C Se
Se
2a
6.9/1
1a
N
O
Me
Cl
N C Se
Se
2
3
4
5
20
32
28
23
4
6.9/1
4.9/1
7.9/1
2.1/1
6.9/1
2b
1b
Me
Cl
N
O
N C Se
Se
2c
1c
N
N
O
N C Se
1d
Se
2d
O
Se
N C Se
1e
2e
N
O
N C Se
1f
Se
6
2f
N
O
a
Isolated yield.
b
Z/E ratio was determined by 1H NMR.
To gain a more detailed insight into the structure, the 1,3-
NaH, THF
0 oC to r.t., 6 h
Se
OH
+
R N C Se
R
oxaselenepane 2a was crystallized from EtOAc–hexane and single
crystals suitable for X-ray analysis were grown by slow evapora-
tion of the solvent.16 An ORTEP drawing, depicted in Figure 1,
shows the molecular structure of the 2a.17 Compound 2a possesses
an exocyclic carbon–nitrogen double bond with Z-configuration.
The bond angle of the selenium atom C1–Se1–C5 was 101.6(2)°.
The length of Se1–C1 bond (1.947(6) Å) is consistent with the typ-
ical Se–C bond (1.94 Å), whereas the bond length of Se1–C5 bond
(1.919(5) Å) is shorter than the typical Se–C bond (1.94 Å).18 The
bond length of C1–N1 in 2a is 1.248(6) Å, which clearly shows that
this is a double bond.
Br
N
O
2
1
Scheme 1.
In conclusion, we report the first synthesis of 1,3-oxaselenepane
derivatives and their Z/E isomerism for the exocyclic C@N bond.
Acknowledgments
This work was supported by a Grant-in-Aid for Science Research
from the Ministry of Education, Culture, Sports, Science, and Tech-
nology of Japan (No. 17550099) for which we are grateful.
References and notes
1. (a) Ogawa, A.; Sonoda, N. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 6, p 461; (b) Ogawa, A.;
Sonoda, N. Rev. Heteroat. Chem. 1994, 10, 43; (c) Guziec, F. S., Jr.; Guziec, L. J. In
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In Comprehensive Organic Functional Group Transformations; Katritzky, A. R.,
Meth-Cohn, O., Rees, C. W., Eds.; Pergamon: Oxford, 1995; Vol. 5, p 565; (e)
Krief, A. In Comprehensive Organometallic Chemistry; Abel, W. W., Stone, F. G. A.,
Wilkinson, G., Eds.; Pergamon: Oxford, 1995; Vol. 11, p 515; (f)Organoselenium
Figure 1. Crystal structure of (Z)-N-(1,3-oxaselenepan-2-ylidene)aniline (2a).
Chemistry:
A Practical Approach; Back, T. G., Ed.; Oxford University Press:
Oxford, 1999.
was obtained only in 4% yield (entry 6). The structures of products
2b–f were determined by comparing the spectral data with those
of 2a. In all cases the Z isomer was the major product. Generally
the selenium containing heterocyclic compounds having an exocy-
clic C@N bond were isolated as the Z isomers only.15 To the best of
our knowledge this is the first time we found the formation of the E
isomer along with the Z isomer.
2. (a) Mehta, S.; Andrews, J. S.; Johnson, B. D.; Svensson, B.; Pinto, B. M. J. Am.
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4. See the review: (a) Murai, T. In Chalcogenocarboxylic Acid Derivatives. In Topics
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504; (b) Heimgartner, H.; Zhou, Y.; Atanassov, P. K.; Sommen, G. L. Phosphorus,
Sulfur Silicon Relat. Elem. 2008, 183, 840.
6. (a) Koketsu, M.; Yamamura, Y.; Ando, H.; Ishihara, H. Heterocycles 2006, 68,
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Koketsu, M.; Sakai, T.; Kiyokuni, T.; Garud, D. R.; Ando, H.; Ishihara, H.
Heterocycles 2006, 68, 1607; (c) Garud, D. R.; Makimura, M.; Ando, H.; Ishihara,
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71.6, 124.0, 128.5, 129.2, 145.2, 158.6; 77Se NMR (95 MHz, CDCl3): d 385.9; MS
(EI): m/z = 289 [M+]; Anal. Calcd for C11H12ClNOSe: C, 45.77; H, 4.19; N, 4.85.
Found: C, 45.47; H, 4.68; N, 5.01.
N-(1,3-Oxaselenepan-2-ylidene)-1-phenylmethanamine (2e): Yield: 23%; IR
(KBr): 1640, 1686 cmÀ1; For Z-isomer 2e: 1H NMR (400 MHz, CDCl3): d 1.86–
1.94 (2H, m, CH2), 2.23–2.31 (2H, m, CH2), 2.96 (2H, t, J = 5.1 Hz,
2J(77Se–1H) = 28.9 Hz, CH2), 4.30 (2H, t, J = 5.1 Hz, CH2), 4.41 (2H, s, CH2),
7.18–7.35 (5H, m, Ar); 13C NMR (125 MHz, CDCl3): d 24.9, 30.1, 30.5, 56.8, 71.0,
126.5, 127.6, 128.3, 139.3, 158.8; 77Se NMR (95 MHz, CDCl3): d 335.1; For E-
isomer 2e: 1H NMR (400 MHz, CDCl3): d 1.86–1.91 (2H, m, CH2), 2.28–2.32 (2H,
m, CH2), 2.89 (2H, t, J = 5.0 Hz, CH2), 4.36 (2H, t, J = 5.0 Hz, CH2), 4.54 (2H, s,
CH2), 7.18–7.25 (5H, m, Ar); 13C NMR (125 MHz, CDCl3): d 24.3, 29.6, 30.8, 52.4,
70.5, 126.4, 127.8, 128.2, 140.3, 156.6; 77Se NMR (95 MHz, CDCl3): d 370.2; MS
(FAB): m/z = 270 [M++1]+; Anal. Calcd for C12H15NOSe: C, 53.74; H, 5.64; N,
5.22. Found: C, 53.93; H, 5.71; N, 5.70.
8. (a) Koketsu, M.; Kiyokuni, T.; Sakai, T.; Ando, H.; Ishihara, H. Chem. Lett. 2006,
35, 626; (b) Koketsu, M.; Yamamura, Y.; Ishihara, H. Synthesis 2006, 2738.
9. (a) Garud, D. R.; Ando, H.; Kawai, Y.; Ishihara, H.; Koketsu, M. Org. Lett. 2007, 9,
4455; (b) Garud, D. R.; Koketsu, M. Org. Lett. 2008, 10, 3319; (c) Nurbaev, K. I.;
Zakhidov, K. A.; Oripov, E. O.; Smiev, R. A.; Shakhidoyatov, K. M. Uzb. Khim. Zh.
1996, 1–2, 96. Chem. Abstr. 1996, 126, 47303; (d) Sommen, G. L.; Linden, A.;
Heimgartner, H. Tetrahedron Lett. 2005, 46, 6723.
10. (a) Barton, D. H. R.; Parekh, S. I.; Tajbakhsh, M.; Theodorakis, E. A.; Tse, C.-L.
Tetrahedron 1994, 50, 639–654; (b) Bakhsh, M. T.; Behshtiha, Y. S.; Heravi, M.
M. J. Chem. Soc. Pak. 1996, 18, 159.
12. Analogous 1,3-oxaselenan-2-imines were readily obtained by the reactions of
isoselenocyanates with 3-chloropropanol. See: Sommen, G. L.; Heimgartner, H.
Pol. J. Chem. 2007, 81, 1413.
13. (a) Murai, T.; Kakami, K.; Hayashi, A.; Komuro, T.; Takada, H.; Fujii, M.; Kanda,
T.; Kato, S. J. Am. Chem. Soc. 1997, 119, 8592; (b) Cullen, E. R.; Guziec, F. S.;
Murphy, C. J.; Wong, T. C.; Andersen, K. K. J. Am. Chem. Soc. 1981, 103, 7055; (c)
Wong, T. C.; Guziec, F. S., Jr.; Moustakis, C. A. J. Chem. Soc., Perkin Trans. 2 1983,
1471.
14. (a) Garreau, M.; Martin, G. J.; Martin, M. L.; Morel, J.; Paulmier, C. Org. Magn.
Reson. 1974, 6, 648; (b) Bartels-Keith, J. R.; Burgess, M. T.; Stevenson, J. M. J. Org.
Chem. 1977, 42, 3725; (c) Wong, T. C.; Engler, E. M. J. Mol. Struct. 1980, 67, 279.
15. (a) Asanuma, Y.; Fujiwara, S.; Shin-ike, T.; Kambe, N. J. Org. Chem. 2004, 69,
4845; (b) Sommen, G. L.; Linden, A.; Heimgartner, H. Eur. J. Org. Chem. 2005,
3127; (c) Zhou1, Y.; Heimgartner, H. Helv. Chim. Acta 2000, 83, 539; (d)
Sommen, G. L.; Linden, A.; Heimgartner, H. Helv. Chim. Acta 2005, 88, 766; (e)
Sommen, G. L.; Linden, A.; Heimgartner, H. Helv. Chim. Acta 2006, 89, 1322; (f)
Atanassov, P. K.; Linden, A.; Heimgartner, H. Heterocycles 2004, 62, 521. Also
see Refs. 6, 7b, 7d, 8a and 9d.
11. Typical synthesis procedure and spectral data of selected compounds. N-(1,3-
oxaselenepan-2-ylidene)aniline (2a): To a stirred solution of NaH (60% in oil,
36.0 mg, 0.90 mmol) in dry THF (2.0 mL) was added phenyl isoselenocyanate
(91 mg, 0.50 mmol) at 0 °C. After 10 min 4-bromobutanol (>80% in THF, 100 lL,
0.75 mmol) was added and stirring was continued for 6 h at rt. The reaction
mixture was quenched with saturated aqueous NH4Cl solution, extracted with
ethyl acetate, and washed with water and brine. The combined organic layer
was dried over sodium sulfate and evaporated to dryness. The residue was
purified by flash chromatography on silica gel with ethyl acetate/n-hexane (1/
10?1/5) as the eluent to give 2a (35 mg, yield 29%, Z/E = 6.9/1). Mp 64–65 °C;
IR (KBr): 1621 cmÀ1; For Z-isomer 2a: 1H NMR (400 MHz, CDCl3): d 1.94–2.00
(2H, m, CH2), 2.23–2.30 (2H, m, CH2), 2.87 (2H, t, J = 5.5 Hz,
2J(77Se–1H) = 29.2 Hz, CH2), 4.43 (2H, t, J = 4.8 Hz, CH2), 6.85 (2H, d, J = 7.4 Hz,
Ar), 7.11 (1H, t, J = 7.4 Hz, Ar), 7.31 (2H, t, J = 7.4 Hz, Ar); 13C NMR (125 MHz,
CDCl3): d 25.2(1J(77Se–13C) = 60.0 Hz), 29.8, 30.5, 71.5, 120.9, 124.2, 128.9,
148.3, 159.9; 77Se NMR (95 MHz, CDCl3): d 361.4; For E-isomer 2a: 1H NMR
(400 MHz, CDCl3): d 1.86–1.91 (2H, m, CH2), 2.28–2.33 (2H, m, CH2), 2.97 (2H, t,
J = 5.5 Hz, 2J(77Se–1H) = 28.5 Hz, CH2), 4.35 (2H, t, J = 4.8 Hz, CH2), 7.03 (2H, d,
J = 8.0 Hz, Ar), 7.05 (1H, t, J = 7.5 Hz, Ar), 7.26 (2H, t, J = 7.4 Hz, Ar); 13C NMR
(125 MHz, CDCl3): d 24.7, 29.3, 30.5, 71.4, 122.4, 123.7, 128.4, 146.7, 157.8;
77Se NMR (95 MHz, CDCl3): d 383.3; MS (EI): m/z = 255 [M+]; HRMS(EI): calcd
for C11H13NOSe: 255.0167, found: 255.0146.
16. X-ray crystallographic data for 2a. Single-crystal X-ray diffraction: Rigaku
AFC7R Mercury CCD area-detector diffractometer using graphite-
monochromated Mo K
a radiation (k = 0.71069 Å). The structures were solved
by direct methods (SIR97, Altomare, A.; Burla, M.; Camalli, M.; Cascarano, G.;
Giacovazzo, C.; Guagliardi, A.; Moliterni, A.; Polidori, G.; Spagna, R. J. Appl.
Crystallogr. 1999, 32, 115) and refined by full-matrix least-squares on F2
(Sheldrick, G. M. SHELEX-97, Program for Crystal Structure refinement,
Universitat Göttingen, 1997). All non-hydrogen atoms were refined
anisotropically and hydrogen atoms were refined by
a riding model.
Empirical absorption corrections were applied. Single crystal was grown
from
EtOAc–hexane:
C11H13NOSe,
Mr = 331.13,
Colorless
crystal
(0.20 Â 0.20 Â 0.15 mm3), Crystal system: Monoclinic, space group: ‘C2/c’,
a = 19.749(16), b = 8.326(6), c = 13.644(11) Å, b = 99.769(12)°, V = 2211(3) Å3,
Z = 8,
l
= 3.36 mmÀ1, F000 = 1024, Dcalcd = 1.527 Mg/m3, Reflections collected:
4-Chloro-N-(1,3-oxaselenepan-2-ylidene)aniline (2c): Yield: 32%; Mp. 96–97 °C;
IR (KBr): 1626 cmÀ1; For Z-isomer 2c: 1H NMR (400 MHz, CDCl3): d 1.94–2.00
(2H, m, CH2), 2.24–2.30 (2H, m, CH2), 2.90 (2H, t, J = 5.5 Hz,
2J(77Se–1H) = 29.2 Hz, CH2), 4.43 (2H, t, J = 4.6 Hz, CH2), 6.78 (2H, d, J = 8.6 Hz,
8747, independent reflections: 2511 unique (Rint = 0.0449), 127 parameters, h
range for data collection 3.2–27.48°. Limiting indices À23h25, À10k10, À17l12,
largest max./mim. in the final difference Fourier synthesis 1.29 e ÅÀ3
/
À0.65 e ÅÀ3, max./min. transmission 0.6323/0.5527, T = 296(2) K, R1 = 0.0777
Ar), 7.26 (2H, d, J = 8.6 Hz, Ar); 13C NMR (125 MHz, CDCl3):
d
25.4
[I > 2r R indices (all data)
(I)], wR2 = 0.1255. Goodness-of-fit on F2 1.192.
(1J(77Se–13C) = 69.9 Hz), 29.8, 30.4, 71.7, 122.3, 129.0, 129.1, 146.3, 160.6;
77Se NMR (95 MHz, CDCl3): d 362.1; For E-isomer 2c: 1H NMR (400 MHz,
CDCl3): d 1.88–1.93 (2H, m, CH2), 2.27–2.34 (2H, m, CH2), 2.98 (2H, t, J = 5.5 Hz,
2J(77Se–1H) = 28.7 Hz , CH2), 4.37 (2H, t, J = 4.6 Hz, CH2), 6.98 (2H, d, J = 8.6 Hz,
Ar), 7.22 (2H, d, J = 8.6 Hz, Ar); 13C NMR (125 MHz, CDCl3): d 24.8, 29.3, 30.4,
R1 = 0.1062, wR2 = 0.1353.
17. CCDC 715134 for 2a contains the supplementary crystallographic data for this
Letter. These data can be obtained free of charge from The Cambridge
Crystallographic Data Center via www.ccdc.cam.ac.uk/data_request/cif.
18. Pauling, L. The Chemical Bond; Cornell University Press: Ithaca, NY, 1976. p 135.