Actinide (Th4+ and UO22+) assisted oxidative coupling of ortho-phenylenediamine in the presence of oxygen

Article abstract of DOI:10.1016/j.tetlet.2015.12.058

While the actinide salts because of their Lewis acidity and flexible coordination geometry demonstrate unique possibilities as catalysts, research with actinide catalysts typically involves complexed organoactinide frameworks. Many actinide salts have yet to be explored in catalysis or as reagents in metal mediated synthesis. Here, the synthesis of the heterocycle 2,3-diaminophenazine has been reported in good yields in the presence of oxygen via the first use of thorium nitrate or uranyl nitrate as the catalyst.

Full text of DOI:10.1016/j.tetlet.2015.12.058

Tetrahedron Letters 57 (2016) 472–475
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
4
+
2+
Actinide (Th and UO ) assisted oxidative coupling of ortho-
2
phenylenediamine in the presence of oxygen
⇑
Branson A. Maynard, Charmaine D. Tutson, K. Sabrina Lynn, Chasity W. Pugh, Anne E. V. Gorden
Auburn University, 179 Chemistry Building, Auburn, AL 36849, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
While the actinide salts because of their Lewis acidity and flexible coordination geometry demonstrate
unique possibilities as catalysts, research with actinide catalysts typically involves complexed organoac-
tinide frameworks. Many actinide salts have yet to be explored in catalysis or as reagents in metal medi-
ated synthesis. Here, the synthesis of the heterocycle 2,3-diaminophenazine has been reported in good
yields in the presence of oxygen via the first use of thorium nitrate or uranyl nitrate as the catalyst.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 30 October 2015
Revised 7 December 2015
Accepted 12 December 2015
Available online 14 December 2015
Keywords:
ortho-Phenylenediamine
Catalysis
Thorium
Actinide
Diaminophenazine
Introduction
in the understanding of the chemistry of the actinides, they require
laborious preparation and, being either air or moisture sensitive,
Recently, the early 5f elements have been of interest for their
potential use in catalysis, metal mediation, and stoichiometric
have short shelf-lives. In contrast to these organoactinide catalysts,
actinide salts offer longer shelf-lives and increased ease of use.
They are commercially available, and still remain to be
characterized.
1
–6
reactivity.
Actinides have 5f valence orbitals and large ionic
radii, both of which offer distinguishing chemical characteristics
7
that can be exploited in catalysis. Reports detailing some of these
The heterocycle 2,3-diaminophenazine (DAP), is of interest in
3
,4,8,9
2,5,10,11
19
synthetic methods
or catalytic reactions
incorporating
the self-assembly of nanobelts, and it is typically prepared via
actinide metals have become more common as new starting mate-
For example, thorium catalysts
have been used for the cyclization and hydroalkoxylation of
2 2
H O catalysis with horseradish peroxidase and fungal laccase
rials have been developed.1
2–14
enzymes. Li took advantage of the electroactivity of DAP when
using the rapid oxidation of OPD to DAP via cupric ion-catalysis
to synthesize electroactive nanoparticles that were to dope a gra-
phene nanolabel. This graphene nanolabel was then coupled with
a peptide-based probe to target SMO, a protein connected to meta-
20
2
⁄
alkynyl alcohols and thorium and uranium Cp complexes have
been used in the ring-opening metathesis polymerization of cyclic
1
1
esters. The focus of this work is typically based on an actinide
center saddled with sterically hindering ligands (such as cyclopen-
pentamethylcyclopentadienyl, or N-ethylmethy-
), although UI has been reported to catalyze Diels–
Alder and Mukaiyama aldol reactions.
static tumor cells that is used as a biomarker, to determine the
1
3
21,22
tadiene,
lamine
metastatic activity of tumor cells.
Non-biological synthetic
1
1,15
3
pathways are known, including catalysis by Fe(III), Co(II), and
16,17
19,23–25
Ultimately, the ligand
Cu(II) metal salts.
We noted that the unencumbered 5f
and the metal are bound covalently to some degree, and the reac-
orbitals of actinide salts may offer another non-biological pathway
to catalyze this synthesis. Here, we describe the thorium nitrate,
uranyl nitrate, and oxygen mediated synthesis of 2,3-diaminophe-
nazine from ortho-phenylenediamine (OPD) (see Scheme 1). Of
note, simple, sterically unencumbered actinide centers have rarely
tivity of these ligand–actinide complexes and their mechanisms of
action have not been fully explained.1
1,15
For example, Arnold and
coworkers have used an organothorium metallacycle precatalyst,
(Me Si) N]Th[k -(N,C)-CH Si(CH )N(SiMe )], to regioselectively
[
3
2
2
2
3
3
1
7,18
oligomerize terminal alkynes producing organic enynes and this
demonstrates the first example of using a Th catalyst such as this
been reported in the literature.
reported with simple actinide salts,1
reactions have been reported using simple thorium salts.
Few reactions have been
7,18,26
and no catalytic
1
8
in C–C bond formation. Although all of these methods have aided
⇑
Corresponding author.
http://dx.doi.org/10.1016/j.tetlet.2015.12.058
040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
0

B. A. Maynard et al. / Tetrahedron Letters 57 (2016) 472–475
473
actinide salt reactions is less than the isolated product in the
4
+
(
Th + O
2
) reaction alone.
To better understand the influence of dioxygen in the mecha-
nism of the oxidation reaction, two reactions were prepared and
allowed to react for seven days. In the first, a Schlenk flask contain-
ing water and ortho-phenylenediamine with Th(NO ) as the acti-
3 4
Scheme 1. Oxidation of ortho-phenylenediamine to 2,3-diaminophenazine.
nide source was degassed by bubbling Argon using a freeze–
pump–thaw method to remove as much dioxygen as possible. In
the second reaction, a Schlenk flask containing water and ortho-
phenylenediamine with UO
degassed using freeze–pump–thaw. After 7 days, no observable
precipitate was present in the reaction flask containing Th(NO
and no color change was observed. No phenazine was detected
upon workup and analysis. The reaction flask with UO (NO
2 3 2
(NO ) as the actinide source was also
3 4
) ,
2
3 2
)
was found to contain 5.2% yield of isolable 2,3-diaminophenazine.
This result indicates that the presence of dioxygen, is needed for
1
6
the oxidation to occur effectively.
A third reaction scheme was initiated to further determine how
vital oxygen was to the reaction scheme. A Schlenk flask was set up
with only a stir bar in an aqueous solution of ortho-phenylenedi-
amine. Argon was bubbled through the solution for two hours,
and then put through three cycles of freeze–pump–thaw in an
2
effort to remove all possible traces of O . This resulted in a 25%
yield of 2,3-diaminophenazine. Thus, it is evident that an oxygen
donor present in the reaction mixture participates in the reaction
Figure 1. Percent yield of oxidative coupling of ortho-phenylenediamine versus
time.
pathway. This result would require the oxygen from H
2
O to serve
as the oxidant. Interestingly, as this reaction contained only H
2
O
and ortho-phenylenediamine, a literature search was unable to find
any previous Letters on the temperature induced oxidation of
ortho-phenylenediamine in an inert atmosphere.
The effect of light on this reaction was explored by running the
3 4
highest yielding actinide salt reaction, with Th(NO ) , in the
absence of light. The reaction was set up in a 250 mL round bottom
flask and heated at 80 °C for 6 days while wrapped in aluminum
foil to block out light. As shown in Figure 2, the absence of light
did not completely quench the reaction and a 33% yield was
obtained as compared to the reaction in the presence of light in
which a yield 92% product was obtained. Thus, as with the actinide
2
and the O previously discussed, light is critical to optimizing the
reaction, indicating that there are likely multiple concurrent reac-
tion pathways and one of these is likely through a radical pathway.
To determine whether or not the reaction proceeds through
interactions with the pi orbitals of the ortho-phenylenediamine
or through interactions with lone pairs of the amines present on
the ortho-phenylenediamine, various substrates were subjected
to the same parameters as the highest yielding actinide catalyzed
reaction. Table 1 outlines the substrates that were explored to
Figure 2. Percent yield of oxidative ortho-phenylenediamine coupling with varying
conditions.
Results and discussion
As shown in Figure 1, dioxygen alone can oxidize ortho-
phenylenediamine to 2,3-diaminophenazine. Incorporating the
simple actinide nitrate salts [Th(NO ) or UO (NO ) ] as a catalyst
3 4 2 3 2
with just 1% catalyst loading, enhances the oxidation of ortho-
3 4
determine if the Th(NO ) would also oxidatively couple them
under these same conditions. To test the effect of the pi orbitals,
reactions with cyclohexene, benzene, and 1,4-cyclohexadiene were
examined. To determine the effect of the lone pairs, aniline, and
catechol were used. Substrates were also reacted in the presence
of ortho-phenylenediamine to determine if the oxidative coupling
of ortho-phenylenediamine was favored. In the presence of ortho-
phenylenediamine, the only product found during analysis was
phenylenediamine to 2,3-diaminophenazine, by factors of 2 and
1
.5, respectively, in the presence of dioxygen. While this oxidation
occurs much slower than results found using simple FeCl salt—in
that case 80% catalyst loading was required (0.48 mmol FeCl to
.60 mmol of ortho-phenylenediamine).19 Here, only a 1% catalyst
loading with Th(NO or UO (NO is required. It is evident that
the addition of actinide ions (Th and UO
3
3
0
2
,3-diaminophenazine, in yields up to 64%. Thorium(IV) nitrate
3
)
4
2
3 2
)
was proven futile as a catalyst to oxidatively couple the substrates
with themselves. Mass spec analysis supported that the reaction
between ortho-phenylenediamine with aniline and ortho-
phenylenediamine with catechol were catalyzed. In both cases,
however, 2,3-diaminophenazine was also synthesized and NMR
analysis did not support the presence of the aniline/ortho-
phenylenediamine product. Thus, for thorium(IV) nitrate reactions,
what was observed is better suited to electron rich environments.
4+
2+
2
) to the aqueous solu-
tion provides metal mediation for the oxidative generation of 2,3-
diaminophenazine. Increasing the Th4 concentration by a factor of
+
2
increases the formation of the 2,3-diaminophenazine product as
seen in Figure 1 (Th and Th run 2). This indicates that the inclusion
4
+
2+
the actinide (Th or UO
2
) ions in the presence of dioxygen exhi-
’ and degassed
bits a synergistic behavior, as the sum of the ‘O
2

4
74
B. A. Maynard et al. / Tetrahedron Letters 57 (2016) 472–475
Table 1
Metal catalyzed oxidative coupling of varying benzene derivatives with ortho-phenylenediamine
Entry
Reagent(s)
Catalyst
Product
Yield (%)
39.5
NH2
N
NH
2
+
1
3
Th(NO )
4
3
4
NH2
N
N
NH2
NH
NH2
2
+
2
3
Fe(NO3)
16.0
64.3
N
N
NH2
NH2
NH2
NH
2
+
3
Th(NO )
NH2
NH2
N
N
NH
NH
2
2
+
4
5
Th(NO
3
)
)
4
4
57.4
N/A
NH2
N
NH2
Th(NO
3
No reaction
NH2
OH
OH
N
NH2
+
NH2
N
N
NH2
OH
*
6
3
Th(NO )
4
30.0
N
OH
NH
OH
OH
7
8
Th(NO
3
)
4
No reaction
N/A
NH2
N
2
NH2
Th(NO
3
)
4
21.0
+
N
NH2
NH2
NH2
9
3
Th(NO )
4
No Reaction
N/A
OH
N
N
NH
NH
2
2
NH2
1
0
1
Th(NO
3
)
4
45.1
+
NH2
OH
1
Th(NO
3
)
4
No reaction
N/A
*
Unable to separate mixture of products.
Conclusions
conditions, safer solvents, and catalysis with good turnover. Funda-
mentally, these observations engage the idea of using the depleted
2
38
While it is tough to argue that incorporating actinide ions into
reaction pathways might result in green or ‘greener’ chemical
methodologies following the principles as outlined by Anastas
actinide reserve, especially depleted
U, as a source for new
routes of metal mediation. Previous Letters in the literature of
phenazine prepared in this fashion feature metals that are able
to go through one electron oxidations [Cu(II) and Co(II)], and the
2
7
and Warner, these reaction conditions allow for mild reaction

B. A. Maynard et al. / Tetrahedron Letters 57 (2016) 472–475
475
proposed mechanisms involved
l-dioxygen with hydrogen perox-
References and notes
ide evolution, the Cu(II) does not clearly report the catalyst loading
2
0
1. Barnea, E.; Eisen, M. S. Coord. Chem. Rev. 2006, 250, 855.
and the Co(II) catalyst loading was much higher, 50%. In our
reaction 40% loading is required for that same yield with the
Cu(II) salts. The mechanism observed in that reaction would be
2
3
.
.
Wobser, S. D.; Marks, T. J. Organometallics 2013, 32, 2517.
Weiss, C. J.; Marks, T. J. Dalton Trans. 2010, 39, 6576.
4. Weiss, C. J.; Wobser, S. D.; Marks, T. J. Organometallics 2010, 29, 6308.
highly unlikely here for either the Th4 or the UO
+
2+
5
6
.
.
Stubbert, B. D.; Marks, T. J. J. Am. Chem. Soc. 2007, 129, 4253.
Fox, A. R.; Bart, S. C.; Meyer, K.; Cummins, C. C. Nature (London, U.K.) 2008, 455,
41.
2
ions, as both
metal centers contain complete electronic shells (K, L, M, and N);
also neither ion possess paired or unpaired electrons in the O shell.
Future work will pursue computation analyses to determine what
might be a more reasonable mechanism.
3
7. Andrea, T.; Eisen, M. S. Chem. Soc. Rev. 2008, 37, 550–567.
8. Schelter, E. J.; Morris, D. E.; Scott, B. L.; Kiplinger, J. L. Chem. Commun.
(
Cambridge, U.K.) 2007, 1029.
9.
Kiplinger, J. L.; Pool, J. A.; Schelter, E. J.; Thompson, J. D.; Scott, B. L.; Morris, D. E.
Angew. Chem., Int. Ed. 2006, 45, 2036.
1
1
1
1
0. Hayes, C. E.; Platel, R. H.; Schafer, L. L.; Leznoff, D. B. Organometallics 2012, 31,
732.
1. Barnea, E.; Moradove, D.; Berthet, J.-C.; Ephritikhine, M.; Eisen, M. S.
Organometallics 2006, 25, 320.
General procedure
6
Caution! The U and Th are radioactive, heavy metals and require
special precautions and waste handling.
2. Foyentin, M.; Folcher, G.; Ephritikhine, M. J. Chem. Soc., Chem. Commun. 1987,
494.
In a typical procedure, 4 mmol of substrate(s) was heated at
3. Kiplinger, J. L.; Morris, D. E.; Scott, B. L.; Burns, C. J. Organometallics 2002, 21,
8
0 °C in a round bottom flask with a stir bar and 100 mL of deion-
5978.
ized H O as solvent. Once dissolved, 1% of UO (NO or Th(NO
2
2
3
)
2
3
)
3
14. Eisen, M. S.; Marks, T. J. J. Mol. Catal. 1994, 86, 23.
1
1
1
5. Andrea, T.; Barnea, E.; Eisen, M. S. J. Am. Chem. Soc. 2008, 130, 2454.
6. Collin, J.; Maria, L.; Santos, I. J. Mol. Catal. A: Chem. 2000, 160, 263.
7. Giuseppone, N.; Van De Weghe, P.; Mellah, M.; Collin, J. Tetrahedron 1998, 54,
13129.
was added to the mixture. The reaction was allowed to stir and
heat at 80 °C. When the experiment time had lapsed; the solution
was filtered, the solid was washed with hexanes, and dried in a
vacuum oven.
18. Batrice, R. J.; McKniven, J.; Arnold, P. L.; Eisen, M. S. Organometallics 2015, 34,
4039.
19. He, D.; Wu, Y.; Xu, B.-Q. Eur. Polym. J. 2007, 43, 3703.
Acknowledgments
20. Niu, S. Y.; Zhang, S. S.; Ma, L. B.; Jiao, K. Bull. Korean Chem. Soc. 2004, 25, 829.
2
1. Li, H.; Huang, Y.; Yu, Y.; Li, W.; Yin, Y.; Li, G. Anal. Chem. 2015. http://dx.doi.org/
0.1021/acs.analchem.5b01750. Ahead of Print.
2. Zhou, P.; Liu, H.; Chen, S.; Lucia, L.; Zhan, H.; Fu, S. Molbank 2011, M730.
1
The authors would like to acknowledge the Defense Threat
Reduction Agency for funding this work via #HDTRA1-11-1-0044.
The CRAIC was funded by the Auburn University Intramural Grant
Program (IGP) 2011.
2
23. Nemeth, S.; Simandi, L. I.; Argay, G.; Kalman, A. Inorg. Chim. Acta 1989, 166, 31.
24. Peng, S. M.; Liaw, D. S. Inorg. Chim. Acta 1986, 113, L11.
25. Rosso, N. D.; Szpoganicz, B.; Martell, A. E. Inorg. Chim. Acta 1999, 287, 193.
26. Morss, L.; Edelstein, N. M.; Fuger, J. In The Chemistry of the Actinide and
Transactinide Elements; Springer, 2006; Vol. 1,
27. Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford
Supplementary data
University Press: New York, 1998.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.12.
0
58.