Regioselective ring-opening of aziridines with diselenides and disulfides using the Zn/AlCl3 system

Article abstract of DOI:10.1080/17415993.2011.551938

An efficient Zn/AlCl₃-promoted highly regioselective one-pot procedure has been demonstrated for the synthesis of β-amino selenides and sulfides from a variety of diselenides/disulfides and aziridines by reductive cleavage of Se-Se and S-S bond

Full text of DOI:10.1080/17415993.2011.551938

This article was downloaded by: [Australian National University]
On: 15 January 2015, At: 22:19
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Journal of Sulfur Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gsrp20
Regioselective ring-opening of
aziridines with diselenides and
disulfides using the Zn/AlCl3 system
Barahman Movassagh a & Elaheh Salehi Morovat a
a Department of Chemistry , K.N. Toosi University of Technology ,
PO Box 16315-1618, Tehran , Iran
Published online: 27 Jan 2011.
To cite this article: Barahman Movassagh & Elaheh Salehi Morovat (2011) Regioselective ring-
opening of aziridines with diselenides and disulfides using the Zn/AlCl3 system, Journal of Sulfur
Chemistry, 32:2, 117-122, DOI: 10.1080/17415993.2011.551938
To link to this article: http://dx.doi.org/10.1080/17415993.2011.551938
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Journal of Sulfur Chemistry
Vol. 32, No. 2, April 2011, 117–122
Regioselective ring-opening of aziridines with diselenides and
disulfides using the Zn/AlCl3 system
Barahman Movassagh* and Elaheh Salehi Morovat
Department of Chemistry, K.N. Toosi University of Technology, PO Box 16315-1618, Tehran, Iran
(Received 7 November 2010; final version received 2 January 2011)
An efficient Zn/AlCl3-promoted highly regioselective one-pot procedure has been demonstrated for the
synthesis of β-amino selenides and sulfides from a variety of diselenides/disulfides and aziridines by
reductive cleavage of Se–Se and S–S bonds using the Zn/AlCl3 system in acetonitrile under very mild
conditions.
Keywords: β-amino selenides; β-amino sulfides; diselenides; disulfides; Zn/AlCl3 system
1. Introduction
The impact of organosulfur and organoselenium chemistry on modern organic synthesis is undis-
putable and has played enormous roles in biology and medicine (1). Among them, β-amino
sulfides and selenides are the key building blocks for the synthesis of many bioactive molecules
(2). Examples are thiol proteins and selenocysteine (Se-Cys). Thiol proteins are important in cellu-
lar antioxidant defenses and redox signaling (3); selenocysteine, recognized as the 21st amino acid
in ribosome-mediated protein synthesis, has both a lower pKa and a higher reduction potential than
cysteine itself, which make it very suitable in proteins that are involved in the antioxidant activity
(4). Furthermore, a wide range of organoselenium and organosulfur compounds are now accepted
as useful antibiotics, anticancer, antimicrobial, anti-inflammatory and antiviral agents (5).
The most straightforward method for the preparation of β-amino sulfides involves the regios-
elective ring-opening reaction of aziridines with thiols using base as catalyst (6) or Lewis acids
such as Bi(OTf)3, LiClO4, ZnCl2 and BF3.OEt2 or Bronsted acids such as CF3SO3H have been
employed (7).
*Corresponding author. Email: bmovass1178@yahoo.com
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2011 Taylor & Francis
DOI: 10.1080/17415993.2011.551938
http://www.informaworld.com

118 B. Movassagh and E.S. Morovat
Among the useful and general methods for the preparation of β-amino sulfides, we can cite
those involving the reaction of olefins with benzeneselenenyl chloride and amines (8), addition of
benzene selenol to aziridines in the presence of triethylamine (9) and nucleophilic ring-opening
of aziridine derivatives by attack of either RSeSeR/NaBH4 (10) or PhSeSePh/(n-Bu)3P (11).
Recently, Ganesh and Chandresekaran (12) introduced an efficient procedure for the synthe-
sis of β-amino selenides and sulfides by aziridine ring-opening with selenolate and thiolate
anions derived from diselenides/disulfides in the presence of Rongalite (sodium hydroxymethane-
sulfinate). In another recent report, β-amino selenides were prepared by the ring-opening of
unprotected aziridines using the RSeSeR/Zn/HCl/Et2O biphasic system under an argon atmo-
sphere; however, the yields were moderate (35–83%) for unprotected aziridines and low (33%)
for protected (N-tosyl)aziridine (13).
2. Results and discussion
In continuation of our previous work on the synthetic utility of zinc selenolates and thiolates
(14), we now disclose that zinc selenolate/thiolate, prepared in situ via the reductive cleavage of
diselenide/disulfide in the presence of Zn/AlCl3, is an effective reagent for the nucleophilic ring-
opening of aziridines in a regioselective manner at room temperature under an ambient atmosphere
(Scheme 1).
Simple stirring of diselenides/disulfides 1 with metallic zinc dust in the presence of alu-
minum(III) chloride in dry acetonitrile at 80 ◦C produced the zinc thiolate/selenolate 2. Then,
the mixture was cooled to room temperature followed by addition of N-tosylaziridines 3, which
gave, after workup, the desired products 4/4ꢀ and 5/5ꢀ in high to excellent yields (15). The presence
of aluminum chloride is essential, and in the absence of this Lewis acid, the reaction does not
proceed at all.
Various diselenides were chosen to investigate the ring-opening of different N-tosylaziridines.
The results are summarized inTable 1. In contrast to two recent reports in which dialkyl diselenides
gave a low yield (13) of the ring-opened product, or no product at all even after 24 h (12), our
method gave a high yield (80%) of the corresponding β-amino selenide 4g from the reaction
of aziridine 3a with dibenzyl diselenide (Entry 7, Table 1). As can be seen from Table 1, in the
case of unsymmetrical aziridines, the reaction proceeds with regioselectivity because in all cases
selenolate anions exclusively attack the less hindered carbon of the aziridine to give the single
regioisomer 4 (Scheme 1). The only exception is given by styrene-derived aziridine 3d (Entry 4,
Table 1), where a large proportion (83%) of the other regioisomer (4ꢀd) was detected. This is due
to the partial stabilization of developing a positive charge at the more hindered site of the aziridine.
The versatility of the reaction was explored further by extending the methodology to cleave the
disulfide bond and its utility to the synthesis of β-amino sulfides. As in the case of diselenides,
disulfides can also undergo a reductive cleavage in the presence of the Zn/AlCl3 system. Several N-
tosylaziridines were converted to β-amino sulfides 5/5ꢀ in high to excellent yields by the reaction
of zinc thiolates in acetonitrile at room temperature. The results are tabulated in Table 2. The
Scheme 1. Zn/AlCl3-promoted synthesis of β-amino selenides and sulfides.

Journal of Sulfur Chemistry 119
Table 1. Synthesis of β-amino selenides from diselenides and various aziridines in the presence of Zn/AlCl3
system.
Entry
1
R1Se–SeR1
(PhSe)2
Aziridine
Product
Yield (%)a,b
90 (12)
2
3
(PhSe)2
(PhSe)2
89 (12)
87 (12)
4
5
(PhSe)2
90 (12) (17:83)c
86 (12)
(4-ClC6H4Se)2
6
7
91 (12)
80 (15)
(PhCH2Se)2
Notes: aIsolated yields. bReferences are provided for known compounds. cBased on the 1H NMR data.
unsymmetrical aziridines 3b and 3c underwent ring-opening, exclusively from the less hindered
carbon, while the styrene-derived aziridine 3d gave the opposite regioselectivity in comparison
with 2-alkyl aziridines (Entries 4 and 9, Table 2).
3. Conclusion
In conclusion, the new procedure described here appears to be highly competitive with other
methods reported in the literature, and in some cases better results are obtained, especially in
terms of reaction time and yields (7a, 11, 13). It has been shown that the methods reported here
are very efficient for the ring-opening of aziridines, with high regioselectivity, under simple and
relatively mild conditions.
4. Experimental
4.1. General procedure
A mixture of diselenide/disulfide (0.5 mmol), activated Zn dust (2.5 mmol) and anhydrous AlCl3
(1.0 mmol) was suspended in anhydrous MeCN (5 mL). The mixture was refluxed, with stirring for
1.5–2 h, during which time the zinc powder was almost consumed. Then, the mixture was cooled

120 B. Movassagh and E.S. Morovat
Table 2. Reaction of aziridines with disulfides in the presence of the Zn/AlCl3 system.
Entry
R1S–SR1
Aziridine
Product
Yield (%)a,b
1
(PhS)2
91 (12)
2
3
(PhS)2
(PhS)2
91 (12)
88 (12)
4
5
(PhS)2
93 (12) (29:71)c
87 (16)
(4-ClC6H4S)2
6
7
8
(4-ClC6H4S)2
(4-MeC6H4S)2
(4-MeOC6H4S)2
89 (12)
86 (17)
85 (16)
9
90 (16)
78 (15)
10
(PhCH2S)2
Notes: aIsolated yields. bReferences are given for known compounds. cBased on the 1H-NMR integration values.
to room temperature, the aziridine (1.0 mmol) was added in one portion and stirring was continued
for 1 h at room temperature followed by evporation of the organic solvent. Water (10 mL) was
added to the residue; the organic layer was extracted with CH2Cl2 (2 × 10 mL), dried (Na2SO4)
and evaporated. Preparative TLC (silica gel, n-hexane-EtOAc) yielded the pure products.
5. Selected physical and spectral data
5.1. 2-(Phenylselanyl)-N-tosylcyclohexanamine (Table 1, 4a)
1
White crystals; m.p. 134–135 ◦C; IR (KBr): 3271 cm−1; H NMR (500 MHz, CDCl3): δ 1.15–
1.34 (m, 4H), 1.53–1.71 (m, 2H), 2.04–2.08 (m, 1H), 2.22–2.34 (m, 1H), 2.43 (s, 3H), 2.97–3.03

Journal of Sulfur Chemistry 121
(m, 2H), 5.18 (br d, J = 4.0 Hz, 1H), 7.20–7.38 (m, 7H), 7.75 (d, J = 8.2 Hz, 2H); 13C NMR
(125 MHz, CDCl3): δ 21.5, 23.3, 25.2, 28.3, 32.2, 47.6, 55.8, 128.8, 129.4, 130.6, 130.9, 131.8,
135.4, 138.6.
5.2. 2-Phenyl-2-(phenylselanyl)-N-tosylethanamine (Table 1, 4ꢀd)
Light yellow oil; IR (neat): 3281 cm−1; 1H NMR (500 MHz, CDCl3): δ 2.43 (s, 3H), 3.34–3.40
(m, 2H), 4.14 (t, J = 7.4 Hz, 1H), 4.77 (br t, J = 5.9 Hz, 1H), 7.12–7.14 (m, 2H), 7.20–7.32 (m,
10H), 7.64 (d, J = 8.3 Hz, 2H).
5.3. 1-(4-Chlorophenylselanyl)-3-phenyl-N-tosylpropan-2-amine (Table 1, 4e)
Colorless crystals; m.p. 58–60 ◦C; IR (KBr): 3287 cm−1; 1H NMR (300 MHz, CDCl3): δ 2.33 (s,
3H), 2.60–2.84 (m, 2H), 2.91 (dd, J = 13.5, 6.0 Hz, 1H), 3.08 (t, J = 7.4 Hz, 1H), 3.29–3.48 (m,
1H), 4.85 (d, J = 7.0 Hz, 1H), 6.87–6.89 (m, 2H), 6.97–7.18 (m, 7H), 7.27 (d, J = 8.3 Hz, 2H),
7.38 (d, J = 7.5 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 21.0, 32.9, 39.7, 54.0, 125.9, 126.3,
126.8, 127.9, 128.2, 128.8, 129.1, 129.2, 133.8, 135.9, 136.1, 142.9.
5.4. 1-(1-Naphthylselanyl)-3-phenyl-N-tosylpropan-2-amine (Table 1, 4f)
Light yellow oil; IR (neat): 3274 cm−1; 1H NMR (500 MHz, CDCl3): δ 2.24 (s, 3H), 2.73–2.80
(m, 2H), 2.95 (dd, J = 13.4, 6.3 Hz, 1H), 3.17 (dd, J = 12.5, 4.7 Hz, 1H), 3.39–3.48 (m, 1H),
4.72 (d, J = 7.0 Hz, 1H), 6.85 (d, J = 8.2 Hz, 4H), 7.08–7.13 (m, 3H), 7.30 (m, 2H), 7.33 (t,
J = 8.0 Hz, 1H), 7.48–7.52 (m, 2H), 7.66 (d, J = 6.1 Hz, 1H), 7.79–7.85 (m, 2H), 8.21–8.24 (m,
1H); 13C NMR (125 MHz, CDCl3): δ 31.0, 32.4, 39.9, 54.1, 125.5, 125.9, 126.4, 126.5, 126.7,
127.0, 128.1, 128.4, 128.6, 128.9, 129.0, 129.2, 130.1, 132.5, 133.8, 136.2, 136.3, 142.4.
5.5. 2-(Phenylthio)-N-tosylcyclohexanamine (Table 2, 5a)
White crystals; m.p. 130–131 ◦C; IR (KBr): 3276 cm−1; 1H NMR (300 MHz, CDCl3): δ 1.19–1.43
(m, 4H), 1.52–1.60 (m, 2H), 1.96–2.08 (m, 1H), 2.12–2.23 (m, 1H), 2.42 (s, 3H), 2.91–3.04 (m,
2H), 5.46 (d, J = 4.4 Hz, 1H), 7.20–7.37 (m, 7H), 7.75 (d, J = 8.3 Hz, 2H); 13C NMR (75 MHz,
CDCl3): δ 21.6, 23.2, 24.4, 31.5, 32.1, 51.2, 55.2, 127.3, 127.6, 128.9, 129.6, 132.9, 137.3, 143.3.
5.6. 2-Phenyl-2-(phenylthio)-N-tosylethanamine (Table 2, 5ꢀd)
1
Light yellow oil; IR (neat): 3291 cm−1; H NMR (300 MHz, CDCl3): δ 2.43 (s, 3H), 3.38 (t,
J = 7.4 Hz, 1H), 4.15 (t, J = 7.6 Hz, 1H), 4.81–4.92 (m, 1H), 5.03 (br t, J = 6.5 Hz, 1H), 7.10–
7.33 (m, 12H), 7.64 (d, J = 8.2 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 21.6, 47.1, 52.5, 127.0,
127.1, 127.8, 127.9, 128.9, 129.0, 129.8, 132.6, 136.8, 138.2, 143.5.
5.7. 2-(4-Methoxyphenylthio)-N-tosylcyclohexanamine (Table 2, 5h)
White crystals; m.p. 102–103 ◦C; IR (KBr): 3276 cm−1; 1H NMR (300 MHz, CDCl3): δ 1.15–1.30
(m, 4H), 1.51–1.56 (m, 2H), 1.88–2.00 (m, 1H), 2.07–2.24 (m, 1H), 2.40 (s, 3H), 2.64–2.76 (m,
1H), 2.86–2.97 (m, 1H), 3.76 (s, 3H), 5.61 (d, J = 4.4 Hz, 1H), 6.74 (d, J = 8.6 Hz, 2H), 7.19
(d, J = 8.6 Hz, 2H), 7.26 (d, J = 8.1 Hz, 2H), 7.75 (d, J = 8.1 Hz, 2H); 13C NMR (75 MHz,

122 B. Movassagh and E.S. Morovat
CDCl3): δ 21.5, 23.4, 24.6, 31.5, 32.2, 52.0, 55.1, 55.3, 114.4, 122.5, 127.3, 129.6, 136.3, 137.5,
143.3, 159.8.
5.8. 2-(Naphthalen-2-ylthio)-2-phenyl-N-tosylethanamine (Table 2, 5ꢀi)
Colorless crystals; m.p. 135–136 ◦C; IR (KBr): 3290 cm−1; 1H NMR (300 MHz, CDCl3): δ 2.37
(s, 3H), 3.20–3.35 (m, 2H), 4.21 (t, J = 7.3 Hz, 1H), 4.62 (br s, 1H), 7.14–7.30 (m, 8H), 7.37–
7.55 (m, 4H), 7.56–7.80 (m, 4H);13C NMR (75 MHz, CDCl3): δ 21.2, 47.3, 52.7, 126.1, 126.3,
126.6, 127.3, 127.7, 127.9, 128.2, 128.7, 128.8, 129.4, 130.3, 131.0, 132.4, 133.5, 137.4, 138.6,
143.0.
Acknowledgement
The authors acknowledge the K.N. Toosi University of Technology Research Council for financial support of this work.
References
(1) (a) Wood, T.F.; Gardner, J.H. J. Am. Chem. Soc. 1941, 63, 2741–2742; (b) Bowden, K.; Chana, R.S. J. Chem. Soc.,
Perkin Trans. 2 1990, 2163–2166; (c) Goel, A.; Mazur, S.J.; Fattah, R.J.; Hartman, T.L.; Turpin, J.A.; Huang, M.;
Rice, W.G.; Appella, E.; Inman, J.K. Bioorg. Med. Chem. Lett. 2002, 12, 767–770; (d) Liotta, D. Organoselenium
Chemistry; Wiley: New York, 1987; (e) Back, T.G. Organoselenium Chemistry: A Practical Approach; Oxford
University Press: Oxford, 1999.
(2) (a) Tanner, D.; He, H.M. Tetrahedron 1992, 48, 6079–6086; (b) Dureault, A.; Tranchepain, I.; Depezay, J.C. J. Org.
Chem. 1989, 54, 5324–5330; (c) Pegoraro, S.; Fiori, S.; Cramer, J.; Rudolph-Böhner, S.; Moroder, L. Protein Sci.
1999, 8, 1605–1613; (d) Moroder, R.J. J. Pept. Sci. 2005, 11, 187–214.
(3) Baty, J.W.; Hampton, M.B.; Winterbourn, C.C. Biochem. J. 2005, 389, 785–792.
(4) Stadtman, T.C. Annu. Rev. Biochem. 1996, 65, 83–100.
(5) (a) Lucas, M.A.; Ngugen, O.T.K.; Schiesser, C.H.; Zheng, S.-L. Tetrahedron 2000, 56, 3995–4000; (b) Mugesh,
G.; du Mont, W.W.; Sies, H. Chem. Rev. 2001, 101, 2125–2180; (c) Malmstrom, J.; Jonsson, M.; Cotgreave, I.A.;
Hammarstrom, L.; Sjodin, M.; Engman, L. J. Am. Chem. Soc. 2001, 123, 3434–3440; (d) Nogueria, C.W.; Zeni, G.;
Roch, J.B.T. Chem. Rev. 2004, 104, 6255–6286.
(6) (a)We, J.; Sun, X.; Li,Y. Eur. J. Org. Chem. 2005, 2005, 4271–4275; (b) Maligres, P.E.; See, M.M.;Askin, D.; Reider,
P.J. Tetrahedron Lett. 1997, 38, 5253–5256; (c) Carreaux, F.; Dureault, A.; Depezay, J.C. Synlett 1992, 527–529; (d)
Burgaud, B.G.M.; Horwell, D.C.; Padova, A.; Pritchard, M.C. Tetrahedron 1996, 52, 13035–13050.
(7) (a)Yadav, J.S.; Reddy, B.V.S.; Baishya, G.; Reddy, P.V.; Harshavardhan, S.J. Synthesis 2004, 1854–1858; (b)Yadav,
J.S.; Reddy. B.V.S.; Baishya, G.; Venkatram Reddy, P.; Narsaiah, A.V. Catal. Commun. 2006, 7, 807–810; (c)
Antolini, L.; Bucciarelli, M.; Caselli, E.; Davoli, P.; Forni, A.; Moretti, I.; Prati, F.; Torre, G. J. Org. Chem. 1997,
62, 8784–8789; (d) Wu, J.; Hou, X.L.; Dai, L.X. J. Chem. Soc., Perkin Trans. 1 2001, 1314–1317; (e) Katagiri, T.;
Takahashi, M.; Fujiwara, Y.; Ihara, H.; Uneyama, K. J. Org. Chem. 1999, 64, 7323–7329.
(8) Boivin, S.; Outurquin, F.; Paulmier, C. Tetrahedron Lett. 2000, 41, 663–666.
(9) Ide, N.D.; Galonic, D.P.; Van der Donk, W.A.; Gin, D.Y. Synlett 2005, 2011–2014.
(10) Braga, A.L.; Paixão, M.W.; Marin. G. Synlett 2005, 25, 1675–1678.
(11) Zhang, W.-X.; Ye, K.; Ruan, S.; Chen, Z.-X.; Xia, Q.-H. Chin. J. Chem. 2007, 25, 1758–1761.
(12) Ganesh, V.; Chandresekaran, S. Synthesis 2009, 3267–3278.
(13) Braga, A.L.; Schwab, R.S.; Alberto, E.E.; Salman, S.M.; Vargas, J.; Azeredo, J.B. Tetrahedron Lett. 2009, 50,
2309–2311.
(14) (a) Nazari, M.; Movassagh, B. Tetrahedron Lett. 2009, 50, 438–441; (b) Nazari, M.; Movassagh, B. Synlett 2009,
1803–1805; (c) Movassagh, B.; Shamsipoor, M. Synlett 2005, 1316–1318; (d) Movassagh, B.; Shamsipoor, M.
Synlett 2005, 121–122; (e) Movassagh, B.; Navidi, M. Tetrahedron Lett. 2008, 49, 6712–6714; (f) Movassagh,
B.; Tavoosi, M. Monatsh. Chem. 2008, 139, 251–253; (g) Movassagh, B.; Zakinezhad, Y. Chem. Lett. 2005, 34,
1330–1331; (h) Movassagh, B.; Sobhani, S.; Kheirdoush, F.; Fadaei, Z. Synth. Commun. 2003, 33, 3103–3108.
(15) Barton, D.H.R.; Britten-Kelly, M.R.; Ferreira, D. J. Chem. Soc., Perkin Trans. 1 1978, 1090–1099.
(16) Kamal, A.; Reddy, D.R.; Rajendar Tetrahedron Lett. 2006, 47, 2261–2264.
(17) Luo, Z.-B.; Hou, X.-L.; Dai, L.-X. Tetrahedron: Asymmetry 2007, 18, 443–446.