A mild oxidation of deactivated naphthalenes and anthracenes to corresponding para-quinones by N-bromosuccinimide

Article abstract of DOI:10.1016/j.tetlet.2014.04.088

A new method to synthesize 1,4-naphthoquinone and 9,10-anthraquinone from naphthalene and anthracene functionalized with either -CHO or -COOH groups, using N-bromosuccinimide (NBS) in aqueous N,N-dimethylformamide at 75-80 °C, has been developed. Further, -CN and -CONH₂ functionalized naphthalenes and anthracenes can also be transformed into respective para-quinones in a one pot reaction, after successive acid hydrolysis and subsequent reaction with NBS. We believe that the present finding may serve as a valuable alternative to the classical approaches for the synthesis of polycyclic quinones from polyaromatic carbaldehydes through Dakin oxidation followed by further oxidation of the resulting hydroquinone by heavy metal oxides.

Full text of DOI:10.1016/j.tetlet.2014.04.088

Accepted Manuscript
A mild oxidation of deactivated naphthalenes and anthracenes to corresponding
para-quinones by N-bromosuccinimide
Palani Natarajan, Vinuta Devi Vagicherla, Muthana Thevar Vijayan
PII:
S0040-4039(14)00725-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.04.088
TETL 44550
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
26 February 2014
25 April 2014
27 April 2014
Please cite this article as: Natarajan, P., Vagicherla, V.D., Vijayan, M.T., A mild oxidation of deactivated
naphthalenes and anthracenes to corresponding para-quinones by N-bromosuccinimide, Tetrahedron Letters
(2014), doi: http://dx.doi.org/10.1016/j.tetlet.2014.04.088
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

A mild oxidation of deactivated naphthalenes and anthracenes to
corresponding para-quinones by N-bromosuccinimide
Palani Natarajan,* Vinuta Devi Vagicherla and Muthana Thevar Vijayan
Functional Materials Division, CSIR-Central Electrochemical Research Institute, Karaikudi -
630006, Tamil Nadu, India.
E-mail: pnatarajan@cecri.res.in
TOC
Abstract
A new method to synthesize 1,4-naphthoquinone and 9,10-anthraquinone from
naphthalene and anthracene functionalized with either -CHO or -COOH groups, using N-
bromosuccinimide (NBS) in aqueous N,N-dimethylformamide at 75-80 °C, has been
developed. Further, -CN and -CONH2 functionalized naphthalenes and anthracenes can also
be transformed into respective para-quinones in a one pot reaction, after successive acid
hydrolysis and subsequent reaction with NBS. We believe that the present finding may serve
as a valuable alternative to the classical approaches for the synthesis of polycyclic quinones
from polyaromatic carbaldehydes through Dakin oxidation followed by further oxidation of
the resulting hydroquinone by heavy metal oxides.
1

In our attempt to synthesize 10-bromo-9-anthraldehyde from 9-anthraldehyde (1A) using
N-bromosuccinimide (NBS, 1eq), we obtained 9,10-anthraquinone (AQ, mp 284-287 °C)1 in
23 % yield, whereas 77 % of the substrate (1A) remained as such, even when the reaction
was performed at room temperature. Intrigued by the formation of AQ, we reinvestigated the
reaction using excess amount of NBS (6 eq). Surprisingly, the yield of AQ raised to 95-98 %,
indicating that 1A underwent an oxidative deformylation reaction.2
AQ is normally obtained in a few ways, which rely on metal catalysts, e.g., i) oxidation of
the anthracene or hydroxy-anthracenes with chromium(VI) reagents,3 ii) Lewis acid catalyzed
Friedel-Craft reaction4 between the benzene and the phthalic anhydride,5 iii) Lewis acid
catalyzed Diels-Alder reaction6 between naphthoquinones and butadienes,5,7 iv) oxidative
demethylation reaction of anthraquinone dimethyl ethers using metal complexes such as ceric
ammonium nitrate,8 silver oxide,9 manganese dioxide,10 cobalt(III) fluoride11 and others.3
Although synthesis of AQ from 1A via oxidative demethylation of 9-methoxyanthracenes
and 9,10-dimethoxyanthracenes, mentioned above, involves two or three steps (Dakin
oxidation,12 etherification and subsequent re-oxidation,13 c.f. path b in Scheme 1), this
method has frequently been used, in the syntheses of anthraquinone-based natural products,
drugs, and dyes.3-12,14 This is mainly due to the fact that the methyl-ether precursors are stable
under different reaction conditions and can be readily converted into the desired quinones in
the later stages of multistep organic syntheses.13 Except for the above mentioned multistep
method (path b in Scheme 1), to the best of our knowledge no alternative protocol is
available to synthesize AQ under mild conditions, without using any metal catalysts.15 Thus
we decided to examine the new-found single step oxidative deformylation reaction of 1A into
AQ, as shown in path a of Scheme 1, mediated by NBS,16 which is often used for allylic,17
benzylic18 and arene19 brominations as well as decarboxylative bromination of α,β-
unsaturated carboxylic acids.20 Remarkably, the reaction can be performed without the need
2

of anhydrous solvents and the product can be easily isolated, upon removal of the water
soluble byproduct of scccinimide. 1-21
Scheme 1. Synthetic routes for the 9,10-anthraquinone from the 9-anthraldehyde
path a
CHO
O
NBS
this
aq. DMF, 80 o
C
work
1A
i. H2O2
ii. CH3OH/H+
O
AQ
OH /OCH3
[O]
ref. 12 & 13
path b
Table 1 summarizes the conversion of 1A into AQ, using NBS, performed under different
conditions, namely the quantity of NBS, choice of solvent, duration and the yield obtained.
The reaction did not occur, when it was performed in CH3CN, EtOAc alone or with further
addition of 5 % of water (entries 10, 11, 12). Due to poor solubility, the reaction did not
proceed in non-polar solvents such as CCl4 and DCE (entries 13, 14). The reaction proceeded
well in N,N-dimethylformamide (DMF). Surprisingly, anhydrous DMF did not result in the
desired product formation (entry 6), whereas a mixture of DMF and water (95:5) was found
to be a perfect solvent system for this oxidation reaction using NBS. The reaction occurred
well at 75-80 °C. Upon further increase in reflux condition resulted in unidentified by-
products as well as vigorous evolution of bromine/HBr. Therefore the oxidative
deformylation reaction of 1A into AQ was examined at 75-80 °C in the DMF-water (95:5,
v/v) mixture employing different moles of NBS. When the reaction was performed with 1
mmol of NBS and 1A each, only 24 % of AQ was obtained, leaving most of the substrate as
such. To determine whether excess amounts (>1 eq) of NBS were essential for complete
conversion of 1A into AQ, experiments were conducted with 2-6 eqs of NBS (Table 1). A
mechanistic analysis indicated that four mmol of NBS required for the complete conversion
3

1
of one mmol of 1A into AQ. This was confirmed by the H NMR titration experiments as
well, cf. Figure 1. The easy recognizable singlet of -CHO proton of 1A at δ = 11.54 ppm
gradually disappeared with the concomitant appearance of two new peaks at δ = 7.82 ppm
and δ = 8.31 ppm corresponding to the formation of the AQ.1,23 When NBS concentration
was increased to 4 eqs all proton signals of 1A disappeared entirely with appearance of two
new signals in the aromatic regions (Figure 1), characteristic for AQ.1 Further increase in
NBS (> 4 mmol) resulted significant changes neither in product yield nor in reaction time
(entries 5, 7, 9). However, no reaction happened without NBS (entry 3). Thus the optimized
condition24 for a perfect oxidative deformylation of 1A into AQ (path a of Scheme 1) is
addition of 4 mmol of NBS (either gradually or at once) to a well-stirred solution of the 1A
(1mmol) in DMF-water mixture (95:5, v/v, 8 mL) at room temperature. The resultant
homogeneous solution was heated at 75-80 °C for 3-4 h, during that time the color of the
reaction mixture turned from yellow to brown, and then quenched with 20% aqueous
NaHCO3 (20-30 mL) solution. The mixture was sonicated for 15 min, the insoluble materials
were isolated by filtration. A pure product of AQ (0.96 mmol, 96%) was obtained after
successive recrystallization in ethyl acetate-hexane mixture (20:80, v/v),1,24 cf. IR, 1H and 13C
NMR data furnished in the Supporting Information (SI). It is worthy to mention that the
unreacted NBS and its′ byproduct, succinimide, were removed from the reaction mixture
gently by treating with an aqueous NaHCO3 solution.16
4

Table 1. An oxidative deformylation of 9-anthraldehyde (1A) by NBS at various reaction
conditions. All reactions were performed using 1 mmol of substrate, 1A.
O
O
N
Br
CHO
O
solvent,
O
1A
AQ
Entry NBS
Solvent
Temp. Time Product
(h)
mmol (v/v)
yield (%)
(°C 5)
1
2
1.1
1.1
0
DMF
DMF
75
20
90
75
75
75
75
75
75
80
8
23a
17a
<2b
71
60
72
8
3
4
DMF
DMF
3
5
6
5
5
DMF
dry DMFc
7
16
4
96
<4d
97
7
8
5
4
DMF-H2O (95:5)
DMF-H2O (95:5)
DMF-H2O (95:5)e
CH3CN
CH3CN-H2O (95:5) 90
EtOAc-H2O (95:5) 80
DCE
CCl4
H2O
DMF-H2O (95:5)
DMF-H2O (95:5)
DMF-H2O (95:5)
DMF-H2O (95:5)
4
96
94
8
26
<10
<5
<5
<10
47
9
6
4
4
4
4
4
4
2
3.5
12
12
24
24
24
24
6
10
11
12
13
14
15
16
17
18
19
100
80
100
75
75
80
120
3
4
4
6
3.5
3.5
73
97
76
a Unreacted 1A was recovered (76-80%). b Unreacted 1A was recovered (>95%). c DMF was
d
purified by drying nightlong over barium oxide and vacuum distillation. Reaction was not
complete and 1A remained as such. e Excess solvent required to make homogeneous solution.
5

Figure 1. The 1H NMR (400 MHz) spectroscopic monitoring of 1A into AQ in DMF-d7/D2O
(95:5, v/v) mixture: (a) at beginning of the reaction, (b) after 45 min, (c) after 90 min, (d)
after 135 min, e) after 180 min, and f) after 240 min.
Having established the optimum condition for the oxidative deformylation reaction
with NBS, the methodology was extended to a series of electron deficient anthracene,
naphthalene, and benzene derivatives, which are shown in Table 2. As anticipated, 1-
napthaldehyde (5N) also resulted in 1,4-naphthoquinone (NQ)24 readily in 91 % yield under
same experimental conditions. Similarly, 9-anthracene carboxylic acid (2A) and 1-
naphthalene carboxylic acid (6N) underwent oxidative decarboxylation to result in AQ and
NQ, respectively, in quantitative yields (Table 2). Direct reaction between NBS and the –CN
and –CONH2 functionalized substrates, 3A,25 4A, and 7N, appeared sluggish, nevertheless,
they provided respective para-quinones after hydrolysis by 30% aqueous H2SO4 solution.13
In other words, –CN and –CONH2 functionalized anthracenes (3A and 4A) and naphthalene
(7N) underwent an oxidative decyanation/an oxidative deamidation reaction, followed by
successive acid hydrolysis and reaction with NBS. Interestingly, 9,10-disubstituted
anthracenes 8A25 and 9A as well underwent an oxidative deformylation smoothly under the
optimized conditions yielding the expected AQ. In contrast to the polycyclic arenes (Table
2), the benzene derivatives (10B-16B) were found to be less reactive towards NBS mediated
6

oxidation reactions.2 Among different substrates examined, 13B and 15B furnished expected
1,4-benzoquinone (BQ)24 in low yields, whereas, 10B-12B, 14B and 16B resulted in
corresponding haloarenes under the experimental condition used. Thus the present protocol is
more suitable for the oxidations of electron deficient polycyclic aromatic compounds (Table
2) than the benzene analogues.
7

Table 2. Synthesis of para-quinones via NBS mediated oxidation reactions in aqueous DMF.
S.
No
Substrate a
Product b
Time
(h)
Yield c
(%)
1
2
3
4
1A, R = CHO
2A, R = COOH
3A,d R = CONH2
AQ
AQ
AQ
AQ
4
97
96
94
83
3.5
13
16
4A,d R = CN
R
O
O
NQ
5
6
7
8
5N, R = CHO
6N, R = COOH
NQ
NQ
NQ
16
16
36
91
89
86
7N,d R = CN
CHO
AQ
4
97
Br
8A
9
AQ
3
92
9A
10B
10
11
12
60
72
24
31
<5
56
11B
12B
13B
13
14
36
34
18
36
80
64
17
14B
15B
15
16
42
Br
6
61
H3CO
OCH3
16B
Br
8

a) All reactions were performed in DMF-H2O mixture using 1 mmol of the substrate and 4-
4.2 mmol of NBS. b) Purity of compounds was established by elemental analysis and melting
point determinations. c) Yields were determined from products isolated by silica gel (60-120
mesh) column chromotography. d) Compounds were hydrolysed by aqueous mineral acids
before NBS oxidation.
A plausible reaction mechanism for the oxidative deformylation of 1A into AQ is
shown in Figure 2. We expected to isolate intermediate compounds A, B and C, respectively,
by treatment of 1A (1 mmol) with 1-, 2-, and 3 mmol of NBS. Nevertheless, independent to
NBS concentration, temperature (20-80 °C) and the duration, AQ was obtained as a sole
product in all of these attempts. In presence of 1 mmol of NBS, instead of reacting all starting
materials to form intermediate A (1 mmol), exclusively 25-30% of the 1A underwent all
transformations (Figure 2) and provided 23% of AQ along with 77% of the starting precursor
(1A). Likewise, about 47% and 73% of 1A, respectively, reacted when 2- and 3 mmol of
NBS employed. Obviously, when 4 mmol of NBS were added either by portionwise or all at
once to the reaction mixture containing 1 mmol of the 1A, AQ was obtained quantitatively
(Tables 1 and 2). This indicating both the optimal NBS stoichiometry (Table 1) and the
proposed reaction mechanism are fit to each other (Figures 1 and 2). From these combined
findings it is discernible that once the reaction begins with a molecule, it undergoes
subsequent steps (Figure 2) rapidly until AQ occurs by consuming 4 equivalents of NBS.26
Similar behaviour has been observed on several oxidations27 and substitution reactions.28
In an unambiguous manner all naphthalene derivatives (5N-7N) offered 1,4-
naphthoquinone,24 even there is a possibility for formation of the 1,2-naphthoquinone. This is
because of combined effects of the steric-, the electronic- and the stability factors of the
intermediate/s generated in the reaction, which are hardly predictable due to the finely
balanced situation among them.29 The less reactivity or the non-reactivity of the benzene
derivatives (10B-16B) against NBS oxidation indicates that the reaction intermediates might
9

be unstable or destabilized due to the weak conjugation while compared to the naphthalene
and the anthracene analogues.30
Figure 2. The proposed reaction mechanism for the oxidative deformylation of the 1A into
the AQ. The mechanism proposed by assuming 1 mole of the 1A involves in the reaction.
Number of mole of NBS consumed in each step is highlighted in red.
In summary, we have demonstrated a mild protocol for the oxidation of deactivated
polycyclic aromatic compounds into corresponding para-quinones in excellent yield31,32 by
treatment with NBS in aqueous-DMF. Advantages of this method are cost effective, metal-
free, the moisture and the oxygen involves, simple work-up procedure and so on. Further
studies on synthetic applications of the present protocol for preparations of various
biologically important qninones and the mechanistic investigations are underway in our
laboratories.
10

Acknowledgements
P.N. gratefully acknowledges the financial support of the Department of Science &
Technology (DST), India through INSPIRE Faculty Fellowship [IFA12-CH-62]. V. D. V. is
grateful to CSIR-CECRI for financial support. We are indebted to Dr. Vijayamohanan K.
Pillai and Dr. D. JayaKumar, CSIR-CECRI, for infrastructure facilities, and also to Dr. R.
Natarajan, CSIR-IICB for help in the manuscript preparation.
Supporting Information
Supplementary Information (SI) available: [IR, 1H and 13C NMR spectra].
11

References
(1) The structure of product, 9,10-anthraquinone (AQ), formed from the reaction between
1
9-anthraldehyde and NBS was confirmed by IR, UV-Vis, MS, H- and 13C NMR
spectra. In addition, melting point of synthesized material met with authentic compound
reported in the literature; see: (a) W. Wang, W-J. Zhang, L. Wang, C. K. Quah, H-K.
Fun, J-H. Xu, Y. Zhang, J. Org. Chem. 2013, 78, 6211; (b) R. Joseph, C. Pulla Rao,
Chem. Rev. 2011, 111, 4658.
(2) The result indicates that the rate of reaction of bromination is lesser than that of
oxidative decarboxylation steps under the experimental condition used; see: (a) L. F.
Fieser, M. J. Haddadin, J. Am. Chem. Soc. 1964, 86, 2392; (b) L. R. Gould, J. R.
Lenhard, S. Farid, J. Phys. Chem. A, 2004, 108, 10949; (c) H. Wang, R. Fan, J. Org.
Chem. 2010, 75, 6994; (d) S. Wertz, A. Studer, Green Chem. 2013, 15, 3116.
(3) (a) R. A. F. Tomas, J. M. Bordado, J. F. P. Gomes, Chem. Rev. 2013, 113, 7421; (b) N.
Seidel, T. Hahn, S. Liebing, W. Seichter, J. Kortus, E. Weber, New J. Chem. 2013, 37,
601.
(4) M. Rueping, B. J. Nachtsheim, Beilstein J. Org. Chem. 2010, 6. 6.
(5) M. Phillips, Chem. Rev. 1929, 6, 157.
(6) V. Nair, R. S. Menon, A. T. Biju, K. G. Abhilash, Chem. Soc. Rev. 2012, 41, 1050.
(7) I. V. Nechepurenko, E. E. Shults, G. A. Tolstikov, Russ. J. Org. Chem. 2003, 39, 1436.
(8) (a) B. M. O’Keefe, D. M. Mans, D. E. Kaelin-Jr., S. F. Martin, J. Am. Chem. Soc. 2010,
132, 15528; (b) M. V. Bhatt, B. Periasamy, Tetrahedron 1994, 50, 3575; (c) K.
Toshima, Y. Maeda, H. Ouchi, A. Asai, S. Matsumura, Bioorg. Med. Chem. Lett. 2000,
10, 2163.
(9) A. I. Reham, A. Elkhair, D. W. Dixon, T. L. Netzel, J. Org. Chem. 2009, 74, 4712.
(10) M. N. Tam, N-H. Nam, G-Z. Jin, B-Z. Ahn, Arch. Pharm. Res. 2000, 23, 283.
(11) G. Cahiez, A. Moyeux, Chem. Rev. 2010, 110, 1435.
(12) (a) M. E. Jung, T. I. Lazarova, J. Org. Chem. 1997, 62, 1553; (b) J. L. Zambrano, D.
Romano, Synlett. 2003, 1545.
(13) (a) C. F. H. Allen, Chem. Rev. 1959, 59, 983; (b) E. Klingsberg, Chem. Rev. 1954, 54,
59; (c) K. Yates, Acc. Chem. Res. 1971, 4, 136; (d) K. G. Hugentobler, F. Rebolledo,
Org. Biomol. Chem. 2014, 12, 615.
12

(14) (a) R. Devulapally, Y-S. Hon, Tetrahedron Lett. 2011, 52, 3183; (b) I. Fujii, Y.
Ebizuka, Chem. Rev. 1997, 97, 2511; (c) R. E. Minto, C. A. Townsend, Chem. Rev.
1997, 97, 2537; (d) Y. Moon, S. Hong, Chem. Commun. 2012, 48, 7191; (e) D. Kim,
M. Min, S. Hong, Chem. Commun. 2013, 49, 4021.
15) M. Gunay, Ed. Eco-Friendly Textile Dyeing and Finishing; HueMetrix Inc: InTech,
2013.
(16) (a) C. Djerassi, Chem. Rev. 1948, 43, 271; (b) R. Filler, Chem. Rev. 1963, 63, 21; (c) O,
G. Mancheno, O. Bistri, C. Bolm, Org. Lett. 2007, 9, 3809; (d) D. W. Kim, H. Y. Choi,
K. J. Lee, D. Y. Chi, Org. Lett. 2001, 3, 445; (e) C. B. Tripathi, S. Mukherjee, J. Org.
Chem. 2012, 77, 1592; (f) W. Baik, H. J. Lee, J. M. Jang, S. Koo, B. H. Kim, J. Org.
Chem. 2000, 65, 108; (g) A. S. Mayhoub, A. Talukdar, M. Cushman, J. Org. Chem.
2010, 75, 3507; (h) X.-L. Wu, J.-J. Xia, G.-W. Wang, Org. Biomol. Chem. 2008, 6,
548; (i) X. Zong, Q.-Z. Zhenga, N. Jiao, Org. Biomol. Chem. 2013, DOI:
10.1039/C3OB42118J.
(17) (a) S. Wolfe, D. V. C. Awang, J. Am. Chem. Soc. 1967, 89, 5287; (b) J. C. Day, M. J.
Lindstrom, P. S. Skell, J. Am. Chem. Soc. 1974, 96, 5616.
(18) (a) D. D. Tanner, N. H. Nam, J. Org. Chem. 1987, 52, 4686; (b) R. P. Hanzlik, A. R.
Schaefer, J. B. Moon, C. M. Judson, J. Am. Chem. Soc. 1987, 109, 4926; (c) S. R. K.
Pingali, S. K. Upadhyaya, B. S. Jursic, Green Chem. 2011, 13, 928; (d) A. Podgorsek,
S. Stavber, M. Zupan, J. Iskra, Tetrahedron 2009, 65, 4429.
(19) (a) N. C. Ganguly, P. De, S. Dutta, Synthesis 2005, 1103; (b) E. J. Corey, M. Ishiguro,
Tetrahedron Lett. 1979, 20, 2745; (c) K. Rajesh, M. Somasundaram, R. Saiganesh, K.
K. Balasubramanian, J. Org. Chem. 2007, 72, 5867; (d) G. K. S. Prakash, T. Mathew,
D. Hoole, P. M. Esteves, Q. Wang, G. Rasul, G. A. Olah, J. Am. Chem. Soc. 2004, 126,
15570.
(20) (a) J. Prakash, S. Roy, J. Org. Chem. 2002, 67, 7861; (b) C. Kuang, Q. Yang, H.
Senboku, M. Tokuda, Synthesis 2005, 1319.
(21) (a) D. V. Pratt, F. Ruan, P. B. Hopkins, J. Org. Chem. 1987, 52, 5053; (b) P. M. Deya,
M. Dopico, A. G. Raso, J. Morey, J. M. Saa, Tetrahedran 1987, 43, 3523.
(22) (a) C. Reichardt, Chem. Soc. Rev. 1992, 21, 147; (b) E. Buncel, S. Rajagopal, Acc.
Chem. Res. 1990, 23, 226.
(23) Z. Song, H. Zhan, Y. Zhou, Chem. Commun. 2009, 448.
13

(24) General Aspects. Solvents were distilled prior to use and millipore water was used for
the reaction. All commercial chemicals such as 1A, 2A, 4A, 5N, 6N, 7N, 9A, 10B, 11B,
12B, 13B, 14B, 15B and 16B were used as received, however, compounds 3A and 8A
were synthesized according to the literature reported protocols.25 All reactions were
carried out in an open atmosphere without any precaution. Reactions were monitored
by analytical thin layer chromatography (TLC) on silica gel. The products were isolated
by column chromatography with silica gel (60-120 mesh). NMR spectra (400 MHz)
were recorded in deuterated solvents. Chemical shifts are reported in δ-scale (ppm) and
are referenced to the residual protiated solvent.
General procedure for the preparation of para-quinones.
To a stirred solution of starting compound (0.5-1.2 mmol) in DMF-H2O (95:5, v/v, 8-
12 mL) mixture was added NBS (4.0-4.2 mmol) at room temperature. The contents
were stirred at room temperature about 10 minutes and then heated for appropriate
duration mentioned in the Table 2. Progress of the reaction in every case was monitored
by TLC analysis. After completion of the reaction, the reaction mixture was cooled to
room temperature and quenched with aqueous NaHCO3 (20%, 20-30 mL) solution. The
insoluble precipitate was isolated by filtration and dried in vacuo. It was further purified
by either recrystallization with ethyl acetate/n-hexane mixture or short pad silica gel
column chromatography led to pure product.
The –CN and −CONH2 functionalized compounds (3A, 4A and 7N) were treated with
aqueous H2SO4 for 8-12 h before NBS mediated oxidation into quinones.
9-anthramide (3A).25 Fair yellow Solid; mp >250 °C; IR (KBr cm-1) 1389, 1608, 1658,
1
3199, 3353; H NMR (CD3OD, 400 MHz) δ 7.64-7.72 (m, 6H), 8.01 (d, 2H, J = 8.1
Hz), 8.21 (d, 2H, J =8.1 Hz), 8.52 (s, 1H).
10-bromo-9-anthraldehyde (8A). Yellow solid; mp 207-211 °C (lit. 208 °C);25d 1
H
NMR (CDCl3, 400 MHz) δ 7.63-7.76 (m, 4H), 8.61-8.69 (m, 2H), 8.85-8.93 (m, 2H),
11.52(s, 1H); 13C NMR (CDCl3, 100 MHz) δ 123.3, 124.1, 125.4, 128.9, 129.0, 130.8,
131.4, 135.0, 192.9.
9,10-anthraquinone (AQ). Yellow solid; mp 284-287 °C (lit. 286 °C);1 IR (KBr, cm−1)
1
3701, 3071, 1968, 1745, 1674, 1580, 1325, 1286; H NMR (CDCl3, 400 MHz) δ 7.80-
13
7.82 (m, 4H), 8.31-8.33 (m, 4H); C NMR (CDCl3, 100 MHz) δ 128.2, 134.4, 135.1,
184.2; MS-EI m/z (%) 208.1 (100). Anal. Calcd for C14H8O2: C, 80.76; H, 3.87; O,
15.37. Found: C, 80.74; H, 3.84.
1,4-naphthoquinone (NQ). Yellow solid; mp 124-128 °C; IR (KBr, cm−1) 3703, 3308,
1
3058, 2961, 1981, 1752, 1660, 1588, 1295; H NMR (CD3OD, 400 MHz) δ 6.98 (s,
2H), 7.73-7.78 (m, 2H), 8.01-8.08 (m, 2H).
1,4-benzoquinone (BQ). Yellow solid; mp 114-116 °C; IR (KBr, cm−1) 3634, 3227,
2710, 2590, 1869, 1718, 1631, 1469, 1356, 1209; 1H NMR (CD3OD, 400 MHz) δ 6.78.
(25) (a) J. S. Meek, D. R. Wilgus, J. R. Dann, J. Am. Chem. Soc. 1960, 82, 2566; (b) D. H.
Burns, J. D. Miller, H-K. Chan, M. O. Delaney, J. Am. Chem. Soc. 1997, 119, 2125; (c)
M. Frédéric, A. Gilles, L. Claude, Synthesis 2006, 2, 293.
14

(26) L. C. Anderson, H. W. Pinnick, J. Org. Chem. 1978, 43, 3417.
(27) (a) A. Chanda, V. V. Fokin, Chem. Rev. 2009, 109, 725; (b) K. Tanaka, F. Toda, Chem.
Rev. 2000, 100, 1025.
(28) H. Abduljabbar, Ed. Steroids – Basic Science; InTech, 2012.
(29) (a) J. M. Sad, J. Morey, C. Rubido, J. Org. Chem. 1986, 51, 4471; (b) P. S. Bailey, S. S.
Bath, F. Dobinson, F. J. Garcia-Sharp, C. D. Johnson, J. Org. Chem. 1964, 29, 697; (c)
U. A. Spitzer, D. G. Lee, J. Org. Chem. 1974, 39, 2468.
(30) (a) N. L. Holy, Chem. Rev. 1974, 74, 243; (b) R. F. Guignard, S. Z. Zard, Chem.
Commun. 2011, 47, 12185.
(31) (a) Z. Shi, C. Zhang, C. Tang, N. Jiao, Chem. Soc. Rev. 2012, 41, 3381; (b) N. Mora-
Diez, S. Keller, J. R. Alvarez-Idaboy, Org. Biomol. Chem. 2009, 7, 3682; (c) Z. Zhang,
G.-W. Wang, C.-B. Miao, Y.-W. Dong, Y.-B. Shen, Chem. Commun. 2004, 1832.
(32) (a) P. Stang, V. V. Zhdankin, Chem. Rev. 1996, 96, 1123; (b) T. Miura, K. Nakashima,
N. Tada, A. Itoh, Chem. Commun. 2011, 47, 1875.
15