Reaction of active methylene groups with 1,2-di(bromoseleno)benzene toward benzo-1,3(2H)-diselenoles

Article abstract of DOI:10.1081/SCC-200054209

The 1,2-di(bromoseleno)benzene has been found to be a bifunctional electrophile able to react with C-H acids. The tandem diselenylation of the active methyle group in β-diketones, β-keto- and β-cyanoesters, diethyl malonate, and malonitrile resulted in the ring closure on the carbon atom. Based on this reaction, 2,2-disubstituted benzo-1,3(2H)-diselenoles, a new group of selenaheterocycles, were obtained in good yields. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200054209

This article was downloaded by: [Flinders University of South Australia]
On: 07 October 2014, At: 04:04
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
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
Reaction of Active Methylene Groups
with 1,2‐Di(Bromoseleno)Benzene toward
Benzo‐1,3(2H)‐Diselenoles
Piotr Potaczek a , Krystian Kloc a & Jacek Młochowski a
a Institute of Organic Chemistry, Biochemistry and Biotechnology , Wrocław
University of Technology , Wyb. Wyspiańskiego, Wrocław, Poland
Published online: 16 Aug 2006.
To cite this article: Piotr Potaczek , Krystian Kloc & Jacek Młochowski (2005) Reaction of Active Methylene
Groups with 1,2‐Di(Bromoseleno)Benzene toward Benzo‐1,3(2H)‐Diselenoles, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 35:8, 1077-1083, DOI:
10.1081/SCC-200054209
To link to this article: http://dx.doi.org/10.1081/SCC-200054209
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

Synthetic Communicationsw, 35: 1077–1083, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200054209
Reaction of Active Methylene Groups with
1,2-Di(Bromoseleno)Benzene toward
Benzo-1,3(2H)-Diselenoles
Piotr Potaczek, Krystian Kloc, and Jacek Młochowski
Institute of Organic Chemistry, Biochemistry and Biotechnology,
´
Wrocław University of Technology, Wyb. Wyspianskiego,
Wrocław, Poland
Abstract: The 1,2-di(bromoseleno)benzene has been found to be a bifunctional elec-
trophile able to react with C-H acids. The tandem diselenylation of the active
methylene group in b-diketones, b-keto- and b-cyanoesters, diethyl malonate, and
malonitrile resulted in the ring closure on the carbon atom. Based on this reaction,
2,2-disubstituted benzo-1,3(2H)-diselenoles, a new group of selenaheterocycles,
were obtained in good yields.
Keywords: 1,2-di(bromoseleno)benzene, benzo-1,3(2H)-diselenoles, selenium
compounds, 1,3-diketones, diethyl malonate
During the past three decades, organoselenium compounds have been exten-
sively applied in organic and material synthesis, ligand chemistry, and
biologically relevant processes.[1–5] Some of them have been found to be
deactivators of active oxygen species present in the living cells[6,7] as well
as catalysts able to transfer oxygen from hydroperoxides to organic substrates
in nonenzymatic conditions.[8]
Our ongoing interest in the chemistry of organoselenium compounds has
been focused on the reactions resulting in the ring closure and formation of the
Received in Poland December 8, 2004
Address correspondence to Jacek Młochowski, Institute of Organic Chemistry, Bio-
´
chemistry and Biotechnology, Wrocław University of Technology, Wyb. Wyspians-
kiego 27, 50-370, Wrocław, Poland. E-mail: jacek.mlochowski@pwr.wroc.pl

1078
P. Potaczek, K. Kloc, and J. Młochowski
selenium-containing heterocycles such as benzisoselenazol-3(2H)-ones and
their azaanalogues,[9–11] 1,3,2-benzothiaselenazoles, benzo[b]selenophen-
3(2H)-ones, and benzo[b]selenophenes.[12,13] Two other new groups of
azaselenaheterocycles, 1,2,4-benzoselenadiazin-3(4H)-ones and 1,3,2-benzo-
diselenazoles (1), have also been obtained in our laboratory.[14]
The compounds 1 were formed in the tandem diselenenylation of primary
amino groups of aliphatic amines with 1,2-di(bromoseleno)benzene (2). This
reagent has two electrophilic selenium atoms and acted as selenenylating
agent. It is also known that another selenium-containing biselectrophile
2-(chloroseleno)benzoyl chloride in similar reactions gives benzisoselena-
zol-3(2H)-ones.[9,10] Moreover, the reaction of this chloride with compounds
that have active methylene groups resulted in tandem diselenylation of
carbon atoms and formation of benzo[b]selenophene ring systems. Although
selenenylation of a-carbon atoms in the carbonyl compounds with chlorosele-
nobenzene is a well-known reaction, to our knowledge diselenenylation of the
same carbon atom remained unknown.
This begs a question: Is diselenenylation of the methylene group activated
by a electron-withdrawing substituent possible when 1,2-di(haloseleno)ben-
zene is a selenenylating agent? If so, a new group of selenium heterocycles,
benz-1,3(2H)-diselenoles (3), could be obtained in this way, as shown in
Scheme 1. The compounds 3 that have a 1,3-diselenide moiety can be
regarded as selenacetals, whose representatives were reported earlier.[1]
For this purpose, 1,2-di(bromoseleno)benzene (2) has been used as the
selenenylating agent because it is stable and could be easily obtained in a
two-step synthesis starting from 1,2-diiodobenzene. In the first step, 1,2-di-
iodobenzene is treated with dilithium diselenide, generated in situ from
elemental lithium and selenium powder in anhydrous tetrahydrofurane, and
produced poly(bis-1,2-phenylene) diselenide (4) as reported in Ref.[15] In
Scheme 1. R: n-Pr, n-Bu, i-Bu, t-Bu, sec-Bu; X, Y: electron-withdrawing groups.

Active Methylene Group Reactions
1079
the next step, diselenide 4 was brominated with bromine in dichloromethane
to 1,2-(dibromoseleno)benzene (3).
Our investigations presented in this work indicate that simple mono-
ketones such as acetone, cyclohexanone, and cyclopentanone that were treated
with 1,2-di(bromoseleno)benzene (2) remained unreacted. Only bromine
was eliminated from the reagent 2 and poly(bis-1,2-phenylene) diselenide
(4) was formed. The compounds that have methylene groups more activated
by the presence of two electron-withdrawing substituents easily underwent
expected diselenylation. Ring closure took place and 2,2-disubstituted benz-
1,3(2H)-diselenoles (3), presented in Scheme 2, were formed. In this
reaction b-ketoesters gave 2-acyl-2-carbethoxybenz-1,3(2H)-diselenoles
(3a, 3b) whereas b-diketones produced 2,2-diacylbenz-1,3(2H)-diselenoles
Scheme 2.

1080
P. Potaczek, K. Kloc, and J. Młochowski
(3c–i). From b-cyanoester 2-cyano-2-carbethoxybenz-1,3(2H)-diselenole
(3j) was formed and from malonitrile 2,2-dicyanobenz-1,3(2H)-diselenole
(3k) was formed. The products were obtained in satisfactory yields (55–85%).
All reported benzo-1,2(3H)-diselenoles (3) were stable compounds and
could be stored without decomposition for a long time, contrary to some of
their reported earlier analogues, benzo[b]selenophen-3(2H)-ones, which
underwent spontaneous deacylation.[13] Moreover, the elaborated reaction of
1,2-(dibromoseleno)benzene (2) with an activated methylene group is more
versatile than the reaction of the same reagent with a primary amino group,
such as nitrogen nucleophile, which is limited to only aliphatic amines.[14]
EXPERIMENTAL
General
Melting points were measured with a Digital Melting Point Apparatus Electro-
1
thermal IA 9100. H and 13C NMR were measured with a Bruker 300-MHz
spectrometer. IR (KBr pellets or CCl4) were measured with a Perkin-Elmer
2000 FT. All starting materials were purchased from Aldrich Chemical Co.
and Fluka. Poly(bis-1,2-phenylene) diselenide (4) was obtained from 1,2-diiodo-
benzene according to the procedure reported in Ref[11]
.
1,2-(dibromoseleno)benzene (2): A solution of bromine (8.9 g, 56 mmol)
in dry 1,2-dichloromethane (100 mL) was added dropwise to a suspension of
diselenide 4 (11.7 g, 50 mmol) at ice–salt bath temperature in the same solvent
(250 mL) over 1 h. The reaction mixture was stirred at room temperature for
24 h; the solvent and excess bromine were evaporated in vacuo. The residue
was recrystallized from 1,2-dichloromethane to yield pure (2) as bright dark
red plates. Yield 60%. Mp 146–1478C (Ref.[16]: 139–1418C).
Synthesis of Benzo-1,2(3H)-Diselenoles (3), General Procedure
The solution of 1,2-di(bromoseleno)benzene (2) (0.788 g, 2.0 mmol) in dry
dichloromethane (130 mL) was added dropwise over 1.5 h to a stirred and
maintained at ice–salt bath solution of diketone, ketoester, cyanoester,
diethyl malonate or malonitrile (2.1 mmol), and triethylamine (0.6 ml,
0.445 g, 4.4 mmol) in dry dichloromethane (20 mL), and the reaction was
continued for 1.5 h. After the reaction had finished, dichloromethane was
evaporated in vacuo and the residue was separated by silica-gel chromato-
graphy (dichloromethane) to give 3a–k.
2-Acetyl-2-carbethoxybenzo-1,3(2H)diselenole (3a): Yield 66%. Yellow
1
oil. IR (KBr) 1736, 1698 cm21 (CO). H NMR (300 MHz, CDCl3) dH 1.32

Active Methylene Group Reactions
1081
(t, 3H, J ¼ 7.2 Hz, –CH3), 2.60 (s, 3H, –CH3), 4.31 (q, 2H, J ¼ 7.2 Hz,
–CH2–), 7.11 (dd, 2H, J ¼ 5.4 and 3.3 Hz, ArH), 7.22 (dd, 2H, J ¼ 5.4 and
3.3 Hz, ArH); 13C NMR (CDCl3, 300 MHz) dC 13.9, 24.1, 63.7, 125.5,
127.0, 138.2, 168.1, 197.2. Anal. for C12H12O3Se2 calcd.: C, 39.61; H, 3.50.
Found: C, 39.80; H, 3.35.
2-Benzoyl-2-carbethoxybenzo-1,3(2H)-diselenole (3b): Yield 68%. Yellow
1
oil. IR (KBr) 1732, 1682 cm21 (CO). H NMR (300 MHz, CDCl3) dH 1.12
(t, 3H, J ¼ 10.8 Hz, –CH3), 4.23 (q, 2H, J ¼ 10.8 Hz, –CH2–), 7.07–7.13
(m, 2H, ArH), 7.19–7.26 (m, 2H, ArH), 7.43–7.49 (m, 2H, ArH), 7.57–7.62
(m, 1H, ArH), 7.84–7.90 (m, 2H, ArH); 13C NMR dC (CDCl3, 300 MHz) dC
13.6, 63.6, 125.4, 126.9, 128.9, 129.1, 133.9, 137.7, 169.1, 188.3. Anal. for
C17H14O3Se2 calcd.: C, 48.01; H, 3.29. Found: C, 48.13; H, 3.30.
2,2-Dicarbethoxybenzo-1,3(2H)-diselenole (3c): Yield 56%. White prisms.
Mp 56–578C (dichloromethane-hexane). IR (KBr) 1740, 1725, 1714 cm21
1
(CO). H NMR (300 MHz, CDCl3) dH 1.27 (t, 6H, J ¼ 7.2 Hz, –CH3), 4.28
(q, 4H, J ¼ 7.2 Hz, –CH2–), 7.07–7.10 (m, 2H, ArH), 7.19–7.26 (m, 2H,
ArH); 13H NMR (CDCl3, 300 MHz) dC 13.8, 63.6, 125.2, 126.6, 138.0, 167.8.
Anal. for C13H14O4Se2 calcd.: C, 39.76; H, 2.55. found: C, 39.81; H, 2.57.
2,2-Diacetylbenzo-1,3(2H)-diselenole (3d): Yield 65%. White prisms. Mp
1
77–788C (dichloromethane-hexane). IR (KBr) 1708, 1688 cm21 (CO). H
NMR (300 MHz, CDCl3) dH 2.53 (s, 6H, –CH3), 7.09–7.14 (m, 2H, ArH),
7.19–7.26 (m, 2H, ArH); 13H NMR (CDCl3, 300 MHz) dC 26.5, 125.5,
127.1, 137.8, 199.4. Anal. for C11H10O2Se2 calcd.: C, 39.70; H, 3.16.
Found: C, 39.77; H, 3.04.
2-Acetyl-2-benzoylbenzo-1,3(2H)-diselenole (3e): Yield 78%. Orange
prisms. Mp 91–938C (dichloromethane-hexane). IR (KBr) 1688, 1672,
1
cm21 (CO). H NMR (300 MHz, CDCl3) dH 2.51 (s, 3H, –CH3), 6.95–7.04
(m, 2H, ArH), 7.15–7.18 (m, 2H, ArH), 7.38–7.41 (m, 2H, ArH), 7.48–
7.53 (m, 1H, ArH), 7.71 (d, 2H, J ¼ 7.5 Hz, ArH); 13H NMR (CDCl3,
300 MHz) dC 24.4, 125.5, 127.1, 129.0, 129.1, 134.2, 137.8, 191.7, 196.3.
Anal. for C16H12O2Se2 calcd.: C, 48.50; H, 3.01. Found: C, 48.75; H, 3.04.
2,2-Succinylbenzo-1,3(2H)-diselenole (3f): Yield 56%. Orange needles. Mp
1
148–1498C (dichloromethane-hexane). IR (KBr) 1717 cm21 (CO). H NMR
(300 MHz, CDCl3) dH 2.95 (s, 4H, –CH2–), 7.13–7.21 (m, 4H, ArH); 13H
NMR (CDCl3, 300 MHz) dC 34.1, 125.7, 127.6, 136.0, 203.9. Anal. for
C11H8O2Se2 calcd.: C, 39.70; H, 2.69. Found: C, 40.02; H, 2.42.
2,2-Glutarylbenzo-1,3(2H)-diselenole (3g): Yield 71%. Yellow prisms. Mp
184–1868C (dichloromethane-hexane). IR (KBr) 1724, 1698 cm21 (CO).
1H NMR (300 MHz, CDCl3) dH 1.98 (quintet, 2H, J ¼ 6.6 Hz –CH2–),

1082
P. Potaczek, K. Kloc, and J. Młochowski
2.94 (t, 4H, J ¼ 6.6 Hz, –CH2–) 7.07–7.12 (m, 2H, ArH), 7.21–7.26 (m, 2H,
ArH) 13H NMR (CDCl3, 300 MHz) dC 17.8, 36.8, 125.6, 127.1, 136.9, 197.7.
Anal. for C12H10O2Se2 calcd.: C, 42.04; H, 3.18. Found: C, 41.88; H, 2.91.
2,2-(3-Methylglutaryl)benzo-1,3(2H)-diselenole (3h): Yield 73%. Yellow
needles. Mp 197–1988C (dichloromethane-hexane). IR (KBr) 1720, 1695,
cm21 (CO). 1H NMR (300 MHz, CDCl3) dH 1.02 (s, 6H, –CH3), 2.88
(s, 4H, –CH2–), 7.06–7.12 (m, 2H, ArH), 7.21–7.26 (m, 2H, ArH);
13H NMR (CDCl3, 300 MHz) dC 28.0, 30.5, 50.5, 126.0, 127.1, 136.9, 197.6.
Anal. for C14H14O2Se2 calcd.: C, 45.20; H, 3.50. Found: C, 45.17; H, 3.76.
2,2-(1,2-Phthalyl) benzo-1,3(2H)-diselenole (3i): Yield 88%. Orange
prisms. Mp 170–1728C (dichloromethane-hexane). IR (KBr) 1710 cm21
1
(CO). H NMR (300 MHz, CDCl3) dH 7.16–7.28 (m, 4H, ArH), 7.91–7.97
(m, 2H, ArH), 8.05–8.10 (m, 2H, ArH); 13H NMR (CDCl3, 300 MHz) dC
124.7, 125.2, 127.3, 136.8, 139.4, 193,7. Anal. for C15H8O2Se2 calcd.: C,
47.60; H, 2.19. Found: C, 47.64; H, 2.14.
2-Ethoxycarbonyl-2-cyanobenzo-1,3(2H)-diselenole (3j): Yield 55%.
Yellow prisms. Mp 96–978C (dichloromethane-hexane). IR (KBr)
1
2221 cm21 (CN), 1745 cm21 (CO). H NMR (300 MHz, CDCl3) dH 1.34
(t, 3H, J ¼ 7.00 Hz, –CH3), 4.38 (q, 2H, J ¼ 7.00 Hz, –CH2–), 7.17–7.26
(m, 4H, ArH); 13H NMR (CDCl3, 300 MHz) dC 13.9, 65.2, 125.7, 127.6,
130.7, 136.5, 164.4. Anal. for C11H9O2 NSe2 calcd.: C, 38.24; H, 2.64; N,
3.76. Found: C, 38.27; H, 2.61; N, 4.06.
2,2-Dicyanobenzo-1,3(2H)-diselenole (3k): Yield 84%. Orange prisms. Mp
118–1218C (dichloromethane-hexane). IR (KBr) 2237 cm21 (CN). 1H NMR
(300 MHz, CDCl3) dH 7.27 (s, 4H, ArH); 13H NMR (CDCl3, 300 MHz)
dC113.2, 126.1, 128.6, 135.4. Anal. for. C9H4N2Se2 calcd.: C, 36.11; H,
1.31; N, 9.30. Found: C, 36.26; H, 1.36; N, 9.40.
ACKNOWLEDGMENTS
This work was supported by the Polish State Committee for Scientific
Research (Grant No. 3T09A 003 27).
REFERENCES
1. Paulmier, C. Selenium Reagents and Intermediates in Organic Synthesis;
Pergamon Press: Oxford, 1986.
2. Tiecco, M. Electrophilic selenium, selenocyclizations. Topics Curr. Chem. 2000,
208, 7–54.

Active Methylene Group Reactions
1083
3. Iwaoka, M.; Tomoda, S. Benzeneselenenyl chloride. In Encyclopedia of Reagents
for Organic Synthesis; Paquette, L., Ed.; Wiley: Chichester, 1994; Vol. 1,
pp. 261–265.
4. Procter, D. J. The synthesis of thiols, selenols, sulfides, selenides, sulfoxides,
selenoxides, sulfones and selenones. J. Chem. Soc. Perkin Trans 1 2000, 6,
835–871.
5. Wirth, T. Chiral selenium compounds in organic synthesis. Tetrahedron 1999,
55 (1), 1–28.
6. Mugesh, G.; Singh, H. B. Synthetic organoselenium compounds as an tioxidants:
Glutathione peroxidase activity. Chem. Soc. Rev. 2000, 29 (5), 347–357.
7. Mugesh, G.; du Mont, W.-W.; Sies, H. Chemistry of biologically important
synthetic organoselenium compounds. Chem. Rev. 2001, 101 (7), 2125–2179.
´
8. Młochowski, J.; Brza¸szcz, M.; Giurg, M.; Palus, J.; Wojtowicz, H. Selenium-
promoted oxidation of organic compounds: reaction and mechanisms. Eur.
J. Org. Chem. 2003, 22, 4329–4339.
9. Młochowski, J.; Kloc, K.; Syper, L.; Inglot, A. D.; Piasecki, E. Aromatic and
azaaromatic diselenides, benzisoselenazolones and related compounds as immuno-
modulators active in humans: Synthesis and properties. Liebigs Ann. Chem. 1993,
12, 1293–1244.
10. Młochowski, J.; Gryglewski, R.; Inglot, A. D.; Jakubowski, A.; Juchniewicz, L.;
Kloc, K. Synthesis and properties of 2-carboxyalkyl-1,2-benzisoselenazol-
3(2H)-ones and related organoselenium compounds as nitric oxide synthase
inhibitors and cytokine inducers. Liebigs Ann. Chem. 1996, 11, 1751–1755.
11. Kloc, K.; Maliszewska, I.; Młochowski, J. Synthesis of 7-azabenzisoselenazol-
3(2H)-ones: A new group of selenium containing antimicrobials. Synth.
Commun. 2003, 33 (21), 3805–3815.
12. Kloc, K.; Młochowski, J. Synthesis of organoselenium sulfonamides as new
potential cytokine inducers: 2,20-diselenobis(benzenesulfonamides) and and
1,3,2-benzenethiaselenazole 1,1,-dioxides. Eur. J. Org. Chem. 1999, 1, 67–71.
13. Kloc, K.; Młochowski, J. Selenylation-acylation of ketones with 2-chloroseleno-
benzoyl chloride: A novel route to benzo[b]selenophenes. Tetrahedron Lett.
2001, 42 (29), 4899–4902.
´
14. Kloc, K.; Młochowski, J.; Osajda, K.; Syper, L.; Wojtowicz, H. New heterocyclic
selenenamides: 1,2,4-benzoselenadiazin-3(4H)-ones and 1,3,2-benzodiselena-
zoles. Tetrahedron Lett. 2002, 43 (22), 4071–4074.
15. Giurg, M.; Młochowski, J. Oxidative ring contraction of cycloalkanones: A facile
method for synthesis of medium ring cycloalkanecarboxylic acids. Synth.
Commun. 1999, 29 (13), 2281–2291.
16. Lambert, C.; Christiaens, L. Alternative syntheses of dibenzotetraselenafulvalene,
of some of its precursors and of tetraselenoalkenes analogs. Tetrahedron Lett.
1984, 25 (8), 833–834.