An optimized method for the synthesis of 2,6-diaminoanthracene

Article abstract of DOI:10.1016/j.tetlet.2011.07.106

The reduction of 2,6-diaminoanthraquinone to 2,6-diaminoanthracene was examined under a variety of conditions. Direct reduction using zinc powder gave a mixture of the target product and 9,10-dihydro-2,6-diaminoanthracene under all the conditions examined. Protection of the starting amine, followed by borohydride reduction and deprotection, gave the target product in 14-50% yield. Finally, tin powder was used to reduce the anthraquinone to 2,6-diaminoanthrone in quantitative yield. This compound was further reduced to the target 2,6-diaminoanthracene in 55-65% yield.

Full text of DOI:10.1016/j.tetlet.2011.07.106

Tetrahedron Letters 52 (2011) 5083–5085
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An optimized method for the synthesis of 2,6-diaminoanthracene
⇑
Rambhoopal Kantam, Robin Holland, Bhanu Priya Khanna, Kevin D. Revell
Department of Chemistry, Murray State University, Murray, KY 42071, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The reduction of 2,6-diaminoanthraquinone to 2,6-diaminoanthracene was examined under a variety of
conditions. Direct reduction using zinc powder gave a mixture of the target product and 9,10-dihydro-
2,6-diaminoanthracene under all the conditions examined. Protection of the starting amine, followed
by borohydride reduction and deprotection, gave the target product in 14–50% yield. Finally, tin powder
was used to reduce the anthraquinone to 2,6-diaminoanthrone in quantitative yield. This compound was
further reduced to the target 2,6-diaminoanthracene in 55–65% yield.
Received 12 May 2011
Revised 20 July 2011
Accepted 22 July 2011
Available online 30 July 2011
Keywords:
Reduction
Tin
Published by Elsevier Ltd.
Anthraquinone
Anthrone
Anthracene
Anthracenes and larger acenes continue to be the subject of
extensive research in the field of organic semiconductors.1–3 In
the course of our research in this field, we recently identified
2,6-diaminoanthracene (2) as a key intermediate for the produc-
tion of several acene platforms. Surprisingly, even though the cor-
responding 2,6-diaminoanthraquinone (1) is inexpensive and
readily available, there are very few reports describing the prepa-
ration of 2.
chloride (1 M), and aq ammonium sulfate. We examined both clas-
sical heating and microwave methods. None of these yielded sig-
nificant amounts of the product.
We then turned to the procedure of Rabjohns et al., who re-
ported the synthesis of 2 in 40% yield by heating compound 1 to
reflux in 2.5 M aq sodium hydroxide with 9 equiv of zinc for
24 h, followed by filtration and separation from the residual zinc
using Soxhlet extraction.8 While we found this procedure to be sig-
nificantly improved over other methods, in our hands these condi-
tions gave a mixture of compounds 2 and 3 in a ratio of 40:60 with
40% combined yield. It is postulated that differences in the activity
of zinc may account for the discrepancies between our results and
the literature reports.
In order to optimize this synthesis, we examined the effects of
reagent ratio, solvent, and temperature on the ratio of compounds
2 and 3 formed. We found a minimum of 4 equiv of zinc was nec-
essary to drive the reaction to completion,à and that the formation
of side product 3 was observed under all ratios examined (Table 1,
entries 1–4). Although we had postulated that the over-reduction
to compound 3 might be favored at higher temperatures, we found
that reducing the temperature did not improve the ratio of 2:3 (Ta-
ble 1, entries 4–5). Finally, we examined the role of solvent compo-
sition on the rate. While we did not find a strong correlation
between the solvent components and the product ratio, we did note
that (a) the reaction goes to completion much more quickly in 50%
ethanol than in 10% ethanol and (b) the reaction did not go to com-
pletion when ethanol was raised to 80% (Table 1, entries 4, 6 and 7).
Although Criswell reported the reduction of a number of substi-
tuted anthraquinones using sodium borohydride, the amino-
substituted quinones were not examined.4 Another study sug-
gested that compound 2 had been prepared from either borohy-
dride or zinc in aqueous ammonia, but did not provide spectral
evidence for its formation.5 Yanagimoto et al. reported that reduc-
tion using zinc in aqueous ammonia gave 2,6-diamino-9,10-dihy-
droanthracene (3),6,7 while Rabjohns reported that compound 2
could be prepared using powdered zinc in aqueous hydroxide.8 Be-
cause of the potential importance of compound 2, and because of
our need for larger quantities of this material, we wished to opti-
mize the reduction of anthraquinone 1 to anthracene 2 (Scheme 1).
In our initial efforts, we found compound 1 to be unreactive
toward sodium borohydride in isopropanol at reflux temperatures.
We, therefore, turned to the reduction of compound 1 using pow-
dered zinc as a reducing agent. We found the zinc reduction in
aqueous ammonia to be very sluggish, typically yielding 0–10%
conversion to a mixture of 2 and 3 after 24 h at reflux tempera-
tures. We examined the reduction under a number of other solvent
conditions, including water, aq acetic acid (5–50%), aq ammonium
à
⇑
Corresponding author. Tel.: +1 270 809 6540; fax: +1 270 809 6474.
E-mail address: kevin.revell@murraystate.edu (K.D. Revell).
Qualitatively, the completion of this reaction is evidenced by a color change from
deep red to bright yellow.
0040-4039/$ - see front matter Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2011.07.106

5084
R. Kantam et al. / Tetrahedron Letters 52 (2011) 5083–5085
O
O
NH2
NH2
reduce
NH2
+
H2N
H2N
H2N
1
2
3
Scheme 1. Reported reduction products of 2,6-diaminoanthraquinone.
Table 1
Optimization of conditions for zinc reduction
Entry
Conditionsa
Solvent ratio aq
OHÀ:EtOH
Productb (%)
2
3
1
4 equiv zn, reflux, 24 h
6 equiv zn, reflux, 24 h
8 equiv zn, reflux, 24 h
10 equiv zn, reflux, 24 h
8 equiv zn, 60 °C, 16 h
8 equiv zn, reflux, 24 h
8 equiv zn, reflux, 24 h
3:5
1:1
1:1
1:1
1:1
4:1
1:4
60
64
66
69
50
58
64
40
37
35
31
50
42
32d
2c
3c
4c
5
6
7
a
All reactions shown run under inert atmosphere, using 2.5 M NaOH as aqueous component.
Percentage of compound in the mixture determined by 1H NMR in DMSO-d6 (while slightly soluble in chloroform, we found that
b
compound 2 gives a complex NMR spectrum in CDCl3, which resolves into the simple, predicted spectrum in DMSO-d6. This presumably
is due to concentration-dependent aggregation effects in chloroform. As a result, all quantitative studies were conducted in DMSO-d6).
c
Average of 2 runs.
In entry 7, 4% starting compound 1 was also present.
d
We next examined the time required for this reaction. We sus-
Concurrent with the study of one-step reduction conditions de-
scribed above, we also explored several protection–reduction–
deprotection schemes to access compound 2. While compound 1
is very resistant to borohydride reduction (presumably due to
the strongly electron-donating amine groups), we found that if
the amine was protected by either an acyl or a BOC protecting
group, the borohydride reduction went smoothly. Deprotection
then gave the purified target in 50% overall yield using hexanoyl
or 14% overall yield using BOC protecting groups (Scheme 2).§
While these three-step sequences worked smoothly, we still felt
that a reproducible, one-step reduction using an inexpensive metal
should be possible. To this end, we postulated that a metal having a
lower reduction potential might avoid the over-reduction and give
product 2 more cleanly. When iron was substituted for zinc, no
reduction was observed. However, when tin was used, the reduc-
tion was found to proceed smoothly to give 2,6-diaminoanthrone
(5) as the only product in quantitative yield (Scheme 3).** Reduc-
tion of compound 5 using sodium borohydride in the presence of
hydroxide then gives the target compound 2, which is very easily
and reproducibly isolated by vacuum filtration in 55–65% overall
yield and >95% purity on a multi-gram scale reaction.
pected that compound 2 was the initially formed product, and that
it underwent a subsequent 2-electron reduction to produce 3. In
light of this, we postulated that shorter reaction times might en-
hance our production of compound 2. We therefore ran a series
of experiments in which we monitored the reaction progress as a
function of time (Fig. 1). Surprisingly, we found that the rate of for-
mation of 3 is strongly dependent on the concentration of starting
material and the percentage of 3 changes very little after the start-
ing material has been consumed. Further, when we combined pure
compound 2 with 6 equiv of zinc for 24 h under refluxing condi-
tions, we found that no compound 3 was formed. These results
suggest that the primary mechanism for over-reduction of 1 to 3
does not involve compound 2 as an intermediate. Under all condi-
tions of zinc reduction tested, we found the production of com-
pound 3 to be competitive with the formation of compound 2.
§
See Supplementary data for experimental procedures and notes regarding these
syntheses.
⁄⁄
Optimized procedure for synthesis of 2,6-diaminoanthrone: 2,6-Diaminoanthraqui-
none (10.0 g, 42 mmol), tin powder (100 mesh, 29.9 g, 252 mmol), 2.5 M aqueous
NaOH (175 mL) and ethanol (200 mL) were combined in a 500 mL reaction flask and
heated to reflux for 24 h under inert atmosphere. The hot reaction mixture was then
poured into water (1 L) and stirred for 20 min. The resulting solid was filtered and
dried in vacuo to give compound 5 (9.4 g, 100%) as a (color) solid. 1H NMR (400 MHz,
DMSO-d6): d 7.82 (d, J = 13.3 Hz, 1H); 7.27 (d, J = 2.3 Hz, 1H); 7.12 (d, J = 11.0 Hz, 1H);
6.80 (dd, J = 7.8, 2.3 Hz, 1H); 6.58 (dd, J = 8.7, 2.4 Hz, 1H); 6.49 (d, J = 1.8 Hz, 1H); 6.03
(s, 2H); 5.17 (s, 2H); 4.01 (s, 2H). 13C NMR (100 MHz, DMSO-d6): d 183.04, 153.93,
148.42, 144.71, 133.45, 129.85, 129.83, 128.65, 121.70, 120.02, 114.24, 111.52,
110.68, 32.97. HRMS (EI) calcd for C14H12N2O: 224.0949, found 224.0949.
Optimized procedure for the synthesis of 2,6-diaminoanthracene (2): Compound 5
(2.0 g, 8.9 mmol), NaBH4 (2.7 g, 71 mmol), ethanol (40 mL) and aq NaOH (2.5 M,
40 mL) were combined and heated to reflux for 6 h. The hot reaction mixture was
poured into water (200 mL) and stirred vigorously for 15 min. The resulting solid was
filtered and dried to give compound 5 (1.05 g, 57%) as a yellow solid. 1H, 13C NMR, MS
consistent with previously reported spectra.8
Figure 1. Percentages of compounds 1, 2, and 3 in reaction mixture as a function of
time. Reaction conditions: 6 equiv zinc, solvent = 1:1 10% aq NaOH:ethanol, reflux
temperatures, inert atmosphere.

R. Kantam et al. / Tetrahedron Letters 52 (2011) 5083–5085
5085
We found that target compound 2 could be most efficiently pre-
pared through a two-step reduction involving tin, followed by so-
dium borohydride. While this method suffers from several
drawbacks, including the toxicity of tin metal and the need for
two reducing agents, we have found it to be the most reliable
and high-yielding method for the preparation of this compound.
NHPG
1. protect
2. NaBH4
1
PGHN
4a-b
Overall Yields:
deprotect
4a-b
2
PG = hexanoyl 50%
PG = BOC 14%
Acknowledgments
Scheme 2. Preparation of compound 2 through protection–reduction–deprotection
sequences.
This material is based upon work supported by the Kentucky
NASA EPSCoR program, by the National Science Foundation under
CHE-0922033, and by the Murray State University Committee on
Institutional Research.
O
Sn
NH2
NaBH4
1
2
Supplementary data
aq. OH-
H2N
i-PrOH
5
55-65%
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.07.106.
100%
Scheme 3. Preparation of target compound 2 via a two-step Sn/NaBH4 reduction
sequence.
References and notes
1. Zhang, H. C.; Guo, E. Q.; Zhang, Y. L.; Ren, P. H.; Yang, W. J. Chem. Mater. 2009, 21,
5125–5135.
2. Silvestri, F.; Marrocchi, A.; Seri, M.; Kim, C.; Marks, T. J.; Facchetti, A.; Taticchi, A.
J. Am. Chem. Soc. 2010, 132, 6108–6123.
3. Lloyd, M. T.; Anthony, J. E.; Malliaras, G. C. Mater. Today 2007, 10, 34–41.
4. Criswell, T.; Klanderman, B. J. Org. Chem. 1974, 39, 770–774.
5. Lu, Z.; Lord, S. J.; Wang, H.; Moerner, W. E.; Twieg, R. J. J. Org. Chem. 2006, 71,
9651–9657.
6. Yanagimoto, T.; Takimiya, K.; Otsubo, T.; Ogura, F. J. Chem. Soc., Chem. Commun.
1993, 519–520.
In conclusion, the literature presents several conflicting reports
on the reduction products of 2,6-diaminoanthraquinone (1). In our
laboratory, we found that this compound was resistant to reduc-
tion using sodium borohydride. While zinc effectively reduces
the compound in basic aqueous solutions, we obtained a mixture
of the target compound 2 and dihydro analog 3. We found the
over-reduction to the dihydro to be competitive with the reduction
to anthracene under all conditions examined. On the other hand,
reduction using powdered tin stops cleanly at anthrone 5.
7. Takimiya, K.; Yanagimoto, T.; Yamashiro, T.; Ogura, F.; Otsubo, T. Bull. Chem. Soc.
Jpn. 1998, 71, 1431–1435.
8. Rabjohns, M. A.; Hodge, P.; Lovell, P. A. Polymer 1997, 38, 3395–3407.