Superacid-promoted synthesis of polychlorinated dibenzofurans

Article abstract of DOI:10.1016/j.tetlet.2016.06.100

Polychlorinated dibenzofurans have been prepared in one step by the condensations of o-chloranil with arenes in triflic acid. A mechanism is proposed involving formation of a monoprotonated quinone (carboxonium ion), electrophilic attack at the arene, and cyclization of a carbocation intermediate. The chemistry is further examined by spectroscopic and theoretical studies.

Full text of DOI:10.1016/j.tetlet.2016.06.100

Accepted Manuscript
Superacid-promoted synthesis of polychlorinated dibenzofurans
Ahmad Qarah, Makafui Gasonoo, Dat Do, Douglas A. Klumpp
PII:
S0040-4039(16)30779-1
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.06.100
TETL 47827
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Tetrahedron Letters
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14 June 2016
22 June 2016
Please cite this article as: Qarah, A., Gasonoo, M., Do, D., Klumpp, D.A., Superacid-promoted synthesis of
polychlorinated dibenzofurans, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.06.100
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Superacid-promoted synthesis of
polychlorinated dibenzofurans
Ahmad Qarah, Makafui Gasonooa Dat Do, and Douglas A. Klumpp*

1
Tetrahedron Letters
journal homepage: www.els evier.com
Superacid-promoted synthesis of polychlorinated dibenzofurans
Ahmad Qarah,a Makafui Gasonoo,a Dat Do,b and Douglas A. Klumpp*,a
aDepartment of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115.
bDepartment of Chemistry, California State Polytechnic University, Pomona, CA, 91768
dklumpp@niu.edu
dklumpp@niu.edu
ARTICLE INFO
ABSTRACT
Article history:
Received
Polychlorinated dibenzofurans have been prepared in one step by the condensations of o-
chloranil with arenes in triflic acid. A mechanism is proposed involving formation of a
monoprotonated quinone (carboxonium ion), electrophilic attack at the arene, and cyclization of
a carbocation intermediate. The chemistry is further examined by spectroscopic and theoretical
studies.
Received in revised form
Accepted
Available online
Keywords:
Keyword_1
Keyword_2
Keyword_3
Keyword_4
Keyword_5
Keywords: heterocycles; superacid; condensation; dioxins; dibenzofurans
2009 Elsevier Ltd. All rights reserved.
Introduction
Polychlorinated dibenzofurans are a persistent and highly
toxic environmental pollutant.1 They are released into the
environment by a variety of means - often the result of poorly
controlled industrial processes,2 waste incineration,3 and other
routes. The polychlorinated dibenzofurans have been the subject
of a vast number studies related to their toxicology,4 detection
and analytical chemistry,5 and environmental impact.6 Despite
the significance of these substances, they are difficult to
synthesize in a controlled manner. Several approaches have been
made towards their directed chemical synthesis, including the
chlorination of dibenzofuran,7 diazocoupling of chlorinated
arenes,8 and the pyrolysis of chlorinated precursors.9 Each of
these synthetic methods suffers from either low yields or poor
regiocontrol. Given the importance of this class of compounds,
new synthetic methods are highly desirable. New chemistry
leading to polychlorinated dibenzofurans may improve access to
the substances, and moreover, it may provide insights into the
formation of these compounds during industrial processes and in
other environments.
proposed that the superelectrophile 2 or 3 is involved in the
transformation. During the course of our studies, we examined
the chemistry of 1,2-benzoquinones. 1,2,3,4-Tetrachloro-1,2-
benzoquinone (o-choranil, 5) is an inexpensive 1,2-benzoquinone
reagent which is used in variety of organic transformations.13
When o-choranil (5) is mixed with benzene in superacid, the
chlorinated dibenzofuran (6) is formed as the major product in
17% yield (Table 1). The balance of the starting material (5) is
assumed to be lost in polymeric byproduct. Numerous attempts
were made to limit the amount of resinous byproduct, however,
the highest obtained yield was 41% of 1,2,3,4-tetrachloro-
dibenzofuran 6. Despite the low yield of this route, it is a direct
synthetic route and competitive with other published methods for
preparing compound 6. It was observed that initiating the
conversion at low temperature provides a modest improvement in
the yield of product. We reasoned that the low temperature
might suppress polymerization and side-reactions at the initial
stage. Weaker acids (H2SO4 and CF3CO2H) were also used as
the acid catalyst, however useful yields of product 6 were not
obtained.
Results
Over the years, our research group has studied the reactions of
several types of 1,2-dicarbonyl compounds and their chemistry in
superacidic media.10 These compounds often form exceedingly
reactive electrophiles, or superelectrophiles, in highly acidic
media.11 This can occur from double protonation of the carbonyl
groups.
For
example,
acenaphthenequinone
and
aceanthrenequinone were shown to condense with benzene in
high yields in superacid CF3SO3H (triflic acid, eq 1).12 It was

2
Tetrahedron
Table 1. Conversion of o-choranil (5) to 1,2,3,4-
tetrachlorodibenzofuran 6.
significant amount of the starting material remains but the
heptachloro and octachlorodibenzofurans are again formed.
Despite using an excess of the chlorinating reagents, complete
halogenation is not obtained. This suggests an equilibrium
involving chlorination and protolytic dechlorination between
hepotachlorodibenzofuran (19) and octachlorodibenzofuran (20,
eq 5).
Although the yields of these condensation reactions are low,
the conversions are quite novel. For the reaction leading to
With chlorinated arene nucleophiles, some polychlorinated
dibenzofurans could be prepared. For example, chlorobenzene
provides product 7 in good yield (eq 2). Again, temperature is
found to be an important factor. If the reaction is started at low
temperature, then the yield of product 7 is over 50%, but reaction
at room temperature gives just 22% yield of the product.
Products 8 and 9 are formed as an inseparable mixture in 28%
overall yield from o-dichlorobenzene (eq 3). We also attempted
the condensation chemistry with 1,2,3-trichlorobenzene and
1,2,3,4-tetrachlorobenzene, but no polychlorinated dibenzofuran
product 6,
a mechanism is proposed involving carbonyl
protonation and subsequent electrophilic attack at benzene
(Scheme 1). Thus, the quinone (5) is protonated at the carbonyl
group to provide the carboxonium ion 12. Although other 1,2-
dicarbonyl compounds are thought to undergo diprotonation in
superacid-promoted reactions with benzene,10 the involvement of
a supelectrophilic dication (13) is probably not necessary. It has
products could be isolated.
Both bromobenzene and
fluorobenzene also give the expected condensation products (10
and 11) from o-chloranil (5).
Scheme 1.
been shown that monocationic carboxonium ions may react with
benzene when electron-withdrawing substituents are present.15 In
the case of 12, the inductive effects of the chloro substituents and
the adjacent carbonyl group should provide a high level of
electrophilic reactivity at the carboxonium ion center. Reaction
with benzene leads to the oxonium ion 14 which undergoes loss
of water to give the carbocation 15. Intermediate 15 provides a
simple route to the dibenzofuran ring system – cyclization
involving the carbonyl oxygen. The proposed mechanism is not
without precedent. Recently, Lemal and coworkers described
heteroaryl adducts of 5 in which an indole and a pyrrole have
reacted at the carbonyl carbon.16 Musgrave and Webster also
described a remarkably similar cyclization in 70% H2SO4 - as
quinone 16 provides the dibenzofuran 18 in high yield (eq 6).17
This type of transformation was also found to be catalyzed by
AlCl3. The exact nature of the proposed cyclization mechanism
is not clear, but there are two likely scenarios: cyclization of 15
or 17 involves the oxygen lone pair electrons to form the new
carbon-oxygen bond, or cyclization of 15 or 17 involves a
concerted 4π-electron electrocyclization. In the later case, the
In an effort to produce more highly chlorinated products, the
6 and 8/9 were subjected to electrophilic
dibenzofurans
chlorination. Olah and co-workers have previously shown that
N-chlorosuccinimide (NCS) is capable of halogenating even
nitro-substituted arenes in the presence of superacid.14 When
compound 6 is combined with an excess of NCS (6 equivalents)
and triflic acid (20 equivalents), more highly chlorinated
dibenzofurans are obtained (eq 4). Analysis by GC-MS and GC-
FID indicated that both the heptachloro and octachloro-
dibenzofurans are formed (relative yields reported). In the case
of heptachlorodibenzofuran, two isomers are obtained in a 3:1
ratio (see Supporting Information). Even in the presence of
excess NCS, however, there remained some starting material 6
(2%). When compounds 8 or 9 are subjected to chlorination, a

3
transformation would be remarkably similar to the Nazarov
reaction, and as such, the present chemistry would be a rare
example of an oxo-Nazarov cyclization.
Summary
We have found the polychlorodibenzofurans may be prepared
in fair yields by the condensations of o-chloranil with arenes in
the presence of superacid. The chemistry represents a direct
route to a class of compounds of great interest. The condensation
begins with protonation of the carbonyl group – significantly
lowing the LUMO of the quinone structure. The key step in the
transformation involves the cyclization of a carbocation with a
carbonyl group – leading to the dibenzofuran ring system.
Polychlorodibenzofurans have been detected as impurities in o-
chloranil, this study may suggest a possible mechanism of
formation for these impurities.
In order to further characterize the nature of the electrophilic
intermediate for o-chloranil 5, NMR studies were done (Table 2).
The quinone was dissolved in solutions of increasing acidity and
the 13C NMR spectra recorded. In the progression from
chloroform to CF3CO2H (Ho -2.7) to CF3SO3H (Ho -14), the
carbonyl carbons move increasingly downfield. While this is
consistent with a greater degree of protonation, the extent of
protonation is difficult to determine. Interestingly, the superacid
solution produces extra sets of peaks at a significantly higher
chemical shift. These downfield peaks may arise from the fully
protonated species, perhaps with cis/trans isomerism.
Table 2. 13C NMR signals from o-
Table 3. B3LYP 6-311G(d,p) calculated parameters for o-
chloranil 5 and related ions.a
chloranil
(25°C).
5
in varied solutions
The structure of o-chloranil 5 - and its protonated ions – was
further studied using computational methods. The quinone and
its ions were studied at the B3LYP 6-311G(d,p) level of theory
using the Gaussian 09 program suite.18 Additional calculations
were done with the MP2 6-31G and HF 6-311G+(d,p) models for
comparison. Relative energies are for isomeric structures and
they represent the differences in ZPE-corrected energies of the
optimized structures. Among the observations from these
calculations, the LUMO level is found to drop considerably with
each protonation. The quinone (5) itself has a LUMO at -0.17
eV, while the monoprotonated ions (12a,b) have LUMOs in the
range of -0.3 eV and the diprotonaed ions (13a,b) have LUMOs
in the range of -0.5 eV. These data are consistent with the
experimental observation that superacidic conditions are required
for reaction with benzene or halogen-substituted benzene. As a
weak nucleophile, benzene (B3LYP 6-311G(d,p) calculated
HOMO at -0.26 eV) requires a fairly reactive electrophile in
order to react. The calculations show that the LUMOs of the
monoprotonated ions (12a,b) are at a comparable level to the
HOMO of benzene. This likely facilitates the initial steps of the
conversion. The lowering of the LUMO is the most significant
effect of quinone protonation, but modest structural effects are
also seen. The C-O bond is shown to lengthen and the C-Cl bond
shortens with protonation of the carbonyl. This is consistent with
delocalization of the cationic charge, even to the extent that n->π
donation may be occurring at the chloro substituent. Regarding
isomeric structures, 12a,b and 13a,b, the endo stereoisomers
(12a and 13a) exhibit modest stabilization over the exo
stereoisomers (12b and 13b). This may be the result of favorable
hydrogen bonding available in the endo structures.
Acknowledgments
This work was supported by the National Science Foundation
(1300878). We gratefully acknowledge this support.
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Supplementary Material
Experimental procedures, characterization data for new
compounds, computational methods and results.
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Highlights:
•A one step procedure has been developed for the
synthesis of polychlorinated dibenzofurans.
•The chemistry involves a superacid-promoted
condensation reaction of o-chloranil and arenes.
•An unusual carbocation cyclization is proposed for
the conversion.