KF/Al2O3 and PEG-400 as a recyclable medium for the selective α-selenation of aldehydes and ketones. Preparation of potential antimicrobial agents

Article abstract of DOI:10.1016/j.tetlet.2009.09.093

2-Phenylseleno aldehydes and ketones were selectively obtained using solid-supported catalyst (KF/Al₂O₃) and PEG-400 as clean, recyclable medium in good to excellent yields. The method was applied in the preparation of highly functio

Full text of DOI:10.1016/j.tetlet.2009.09.093

Tetrahedron Letters 50 (2009) 6761–6763
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
KF/Al2O3 and PEG-400 as a recyclable medium for the selective a-selenation
of aldehydes and ketones. Preparation of potential antimicrobial agents
Francine Novack Victoria, Cátia S. Radatz, Maraisa Sachini, Raquel G. Jacob, Gelson Perin,
*
Wladimir P. da Silva, Eder J. Lenardão
Instituto de Química e Geociências, LASOL, Universidade Federal de Pelotas, UFPel, PO Box 354, 96010-900 Pelotas, RS, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 July 2009
Revised 16 September 2009
Accepted 17 September 2009
Available online 25 September 2009
2-Phenylseleno aldehydes and ketones were selectively obtained using solid-supported catalyst (KF/Al2O3)
and PEG-400 as clean, recyclable medium in good to excellent yields. The method was applied in the prep-
aration of highly functionalized 2-phenylseleno citronellal and citronellol, potential bactericide agents. The
catalytic system KF/Al2O3 and PEG-400 can be re-used for four times without previous treatment.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
a-Selenylation
Green chemistry
KF/Al2O3
PEG-400
Citronellal
Citronellol
The synthesis of
a
-phenylseleno aldehydes and ketones has
aration and synthetic applications of organochalcogenium com-
pounds.12,13 More recently, we have described several efficient
approaches using KF/Al2O3 and recyclable solvents.13
In continuation to these studies, here we describe the results on
the synthesis of 2-phenylseleno aldehydes and ketones, using KF/
Al2O3 and PEG-400 (Scheme 1, Table 1).14,15
attracted the attention of synthetic organic chemists because they
can be converted to very useful compounds, such as ,b-unsatu-
rated carbonyl,1 -amino acids,2 -hydroxy esters3 and allylic
amines,4 aziridines,5 and alcohols.6 In a general way, the methods
to access -phenylseleno carbonyl compounds consist in the reac-
a
a
a
a
tion of an enolate with an electrophilic organoselenium species or
by substitution reactions involving nucleophilic organoselenium.1
Most of the employed methods use strong bases, such as LDA at
78 °C,1a,b moisture-sensitive zirconium, aluminum,7 and sele-
nium-containing tributylstannyl reagents.8 More recently, the use
Initially, we chose pentanal (1a) and diphenyl diselenide as
standard starting materials to perform the optimization studies
(Table 1). We examined the temperature, amounts of KF/Al2O3
(40%) and solvent, and the use of N2 atmosphere. When a mixture
of 1a (1.0 mmol) and (C6H5Se)2 (1.0 mmol) was stirred in the pres-
ence of 0.32 g of KF/Al2O3 (40%) and PEG-400 (1.0 g) at room tem-
of secondary amines as organocatalysts for the a-selenylation was-
described.9 In recent years, the use of green recyclable systems in
organic syntheses, such as solid-supported catalysts and non-vola-
tile solvents, has been growing.10 In this line, the use of potassium
fluoride supported on alumina (KF/Al2O3) as a green catalytic sys-
tem for a number of transformations has been increased.11 By
using KF/Al2O3, the products can be easily isolated by filtration
and the generation of large amounts of salts at the end of the syn-
thesis, as well as the use of stoichiometric strong bases, can be
avoided. On the other hand, polyethylene glycol (PEG-400) is a
non-toxic, non-volatile, and recyclable solvent whose use in organ-
ic synthesis has been raised in recent years.10b Our major research
goal is the development of new and cleaner protocols for the prep-
perature under N2 atmosphere, no product of a-selenylation was
observed after 24 h (Table 1, entry 1). However, when the same
mixture was heated at 60 °C, 2-phenylseleno pentanal 2a was ob-
tained in 97% yield after stirring for 3 h (Table 1, entry 2). The
atomic efficiency of the reaction was improved using 0.5 mmol of
(C6H5Se)2, giving similar yield of 2a (Table 1, entry 3). Smaller
amounts of the solid-supported catalyst give poor yields of 2a even
after longer reaction times (Table 1, entry 4).
O
O
R
KF/Al2O3, 60 ºC
PEG-400, N2
R
R1
2a-h
(C6H5Se)2
R1
+
C6H5Se
1a-h
* Corresponding author. Tel./fax: +55 53 3275 7533.
E-mail address: lenardao@ufpel.edu.br (E.J. Lenardão).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.09.093

6762
F. N. Victoria et al. / Tetrahedron Letters 50 (2009) 6761–6763
Table 1
Table 2
Optimization of the synthesis of 2-phenylseleno pentanal 2a according to Scheme 1a
Synthesis of 2-phenylseleno aldehydes and ketones 2a–h
Entry
(C6H5Se)2
(equiv)
KF/Al2O3 40%
(g)
Temp.
(°C)
Time
(h)
Yieldb
(%)
Entry
Aldehydes or
ketones 1
Product 2
Time (h)
Yielda (%)
1
2
3
4
5
6
1.0
1.0
0.5
0.5
0.5
0.5
0.32
0.32
0.32
0.10
0.32
0.32
rt
24
3
3
3
24
48
NRc
97
95
60
60
60
rt
C6H5Se
CHO
1
3
95
60
CHO
1a
NRc,d
10d
2a
60
a
b
c
Reaction conditions: pentanal (1a, 1.0 mmol); PEG-400 (1.0 g); N2 atmosphere.
The reaction was followed by TLC and GC until complete consumption of 1a.
No product was detected by GC.
C6H5Se
CHO
2
3
3
3
67
70
d
CHO
Glycerin (1.0 mL) was used as solvent instead of PEG-400.
1b
2b
C6H5Se
Recently, we described the use of glycerin as an efficient recy-
CHO
clable solvent in KF/Al2O3-promoted reactions.12b Thus, we decide
to evaluate this renewable feed-stock as a possible solvent in the
CHO
1c
2c
a-selenylation of pentanal. Unfortunately, no reaction took place
at room temperature and low yield of 2a was obtained after long
reaction time at 60 °C (Table 1, entries 5 and 6).
O
O
SeC6H5
It was also observed that the catalytic system can be re-used for
additional four cycles, just by washing it with hexanes and drying
under vacuum. The product 2a was obtained in 95, 86, 66, 62, and
59% yields after successive cycles.
4
5
6
7
21
21
6
96
70
69
81
1d
2d
O
O
Using the optimized conditions, the protocol was extended with
good results to other aldehydes and ketones (Table 2, entries 2–8).
It was observed that the reaction yields were slightly lower when
aliphatic butanal 1b and propanal 1c were used as aldehydes,
probably due to their fast auto-condensation under the reaction
conditions (Table 2, entries 2 and 3). We also noted that ketones
1d–g require a longer reaction time to afford the respective 2-phe-
nylseleno derivatives 2d–g (Table 2, entries 4–7). Because of our
interest in the development of new, cleaner synthetic methods
using renewable, easily available polyfunctionalized starting mate-
SeC6H5
1e
1f
2e
O
O
O
O
SeC6H5
2f
rials, we use this new protocol in the a-selenylation of (R)-citronel-
lal 1h, a chiral natural terpene isolated from citronella oil.16 In this
case, a 1:1 mixture of syn and anti 2-phenylseleno citronellal 2h
was obtained in 80% yield (Table 2, entry 8).
SeC6H5
14.5
The method described in Scheme 1 was successfully used in the
direct preparation of 2h starting from the essential oil of citronella
(Cymbopogon nardus (L) Rendle). The major component of the
essential oil of citronella, extracted from the plant grown in south-
ern Brazil (Três Passos-RS), was found to be (+)-R-citronellal 1h
(40–51%).17 2-Phenylseleno citronellal 2h was obtained in 71%
yield and unreacted geraniol, citronellol, geranyl acetate, and other
minor constituents of the starting oil were recovered. The protocol
was applied in the one-pot preparation of 2-phenylseleno
citronellol 3 (Scheme 2). Thus, after the formation of 2h was added
2 equiv of NaBH4 and the mixture was stirred at room temperature
for additional 2.5 h affording the alcohol 3 in 73% overall yield
(Table 2, entry 9).
1g
2g
SeC6H5
CHO
CHO
8
9
3
80
73
1h
2h
SeC6H5
OH
CHO
5.5
2-Phenylseleno citronellal 2h and 2-phenylseleno citronellol 3
were screened for their antibacterial activity and preliminary stud-
ies showed activity against Listeria monocytogenes, Staphylococcus
aureus, and Salmonella enteridis. 2-Phenylseleno citronellal 2h
was the more active against the three tested microorganisms, even
compared with the parent citronellal 1h. The antimicrobial activity
presented by 2h was L. monocytogenes > S. enteridis > S. aureus and
for 3 it was S. aureus > S. enteridis > L. monocytogenes.
In conclusion, several 2-phenylseleno aldehydes and ketones
could be prepared using the reusable catalytic system KF/Al2O3
and PEG-400. This eco-friendly protocol can be successfully ap-
plied to the direct synthesis of bactericide agent 2-phenylseleno
citronellal 2h from crude citronella oil.
1h
3
a
Yields of pure products isolated by column chromatography (hexanes/AcOEt)
and identified by mass spectrometry, 1H, and 13C NMR.1,8,9,11b
SeC6H5
OH
1. KF/Al2O3, 60 ºC
PEG-400, N2
(C6H5Se)2
+
CHO
2. NaBH4, r.t.
1h
3
Scheme 2.

F. N. Victoria et al. / Tetrahedron Letters 50 (2009) 6761–6763
6763
12. (a) Perin, G.; Lenardão, E. J.; Jacob, R. G.; Panatieri, R. B. Chem. Rev. 2009, 109,
1277; (b) Lenardão, E. J.; Mendes, S. R.; Ferreira, P. C.; Perin, G.; Silveira, C. C.;
Jacob, R. G. Tetrahedron Lett. 2006, 47, 7439; (c) Perin, G.; Jacob, R. G.; Dutra, L.
G.; Azambuja, F.; Santos, G. F. F.; Lenardão, E. J. Tetrahedron Lett. 2006, 47, 935;
(d) Perin, G.; Mendes, S. R.; Silva, M. S.; Lenardão, E. J.; Jacob, R. G.; Santos, P. C.
Synth. Commun. 2006, 36, 2587; (e) Perin, G.; Jacob, R. G.; Azambuja, F.;
Botteselle, G. V.; Siqueira, G. M.; Freitag, R. A.; Lenardão, E. J. Tetrahedron Lett.
2005, 46, 1679.
13. (a) Lenardão, E. J.; Trecha, D. O.; Ferreira, P. C.; Jacob, R. G.; Perin, G. J. Braz.
Chem. Soc. 2009, 20, 93; (b) Lenardão, E. J.; Silva, M. S.; Sachini, M.; Lara, R. G.;
Jacob, R. G.; Perin, G. ARKIVOC 2009, xi, 221; (c) Silveira, C. C.; Mendes, S. R.;
Líbero, F. M.; Lenardão, E. J.; Perin, G. Tetrahedron Lett. 2009, 50, 6060.
14. Preparation of alumina-supported potassium fluoride:18 Alumina (6.0 g of Al2O3
90, 0.063–0.200 mm, Merck), KFÁ2H2O (5.2 g), and water (10 mL) were mixed
in a 50 mL beaker and the suspension was stirred at 65 °C for 1 h. The resulting
solid was dried at 80 °C for 1 h and subsequently 4 h at 300 °C in an oven and
finally cooled to room temperature in a desiccator. The content of KF is about
40% (m/m).
Acknowledgments
This project is funded by CNPq, CAPES, and FAPERGS.
References and notes
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