Novel Synthesis of 2-Amino-1,4-benzoquinone-4-phenylimides from Anilines via Dess-Martin Periodinane Oxidation

Article abstract of DOI:10.1055/s-2007-984516

A synthetic investigation on oxidation of anilines to 2-amino-1,4-benzoquinone-4-phenylimides via Dess-Martin periodinane (DMP) was carried out. This facile protocol offered the advantage of short reaction times, mild reaction conditions, high yields and compatibility with a wide range of functional groups.

Full text of DOI:10.1055/s-2007-984516

LETTER
1679
Novel Synthesis of 2-Amino-1,4-benzoquinone-4-phenylimides from Anilines
via Dess–Martin Periodinane Oxidation
N
ovel Synthesis of
e
2-Amino-1
n
,4-benzoqui
g
none-4-phenylimid
C
es hang Ma, Xuan Zhen Jiang*
Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang, 310027, P. R. of China
Fax +86(571)87951611; E-mail: chejiang@zju.edu.cn
Received 7 December 2006
conditions (Table 1). It was found that benzene, toluene,
Abstract: A synthetic investigation on oxidation of anilines to 2-
amino-1,4-benzoquinone-4-phenylimides via Dess–Martin periodi-
nane (DMP) was carried out. This facile protocol offered the advan-
tage of short reaction times, mild reaction conditions, high yields
and compatibility with a wide range of functional groups.
CH3CN, CHCl3, and CH2Cl2 were all suitable solvents. In-
terestingly, addition of water accelerated the reaction (en-
tries 3–6). After optimization, we found that using 2.2
equivalents of DMP and two equivalents of water provid-
ed the highest product yield (entry 6).
Key words: iminoquinone, periodinane, oxidation
Table 1 Optimization of Reaction Conditionsa
NH2
N
NH2
O
Iminoquinone is an important moiety of a large number of
antineoplastic drugs and plays a significant role in the
nucleus of actinomycins, which are powerful, highly toxic
natural antibiotics. The antineoplastic activity of these
drugs is the result of a strong interaction with DNA in the
target cells, which causes degradation of the nucleic acid
and, consequently, terminates its biological functions.
The planar structure of these drugs facilitates intercalation
between the DNA base pairs. At the same time, the quino-
ne moiety of these agents can also undergo enzymatic re-
duction.1 Several iminoquinone-based compounds related
to the actinoymcin chromophore have already been syn-
thesized as new anticancer intercalating drugs.2
DMP
1a
1b
Entry DMP Conditions
(equiv)
Time Yield
(min) (%)
1
2
3
4
5
6
1.5
2.0
2.0
2.0
2.0
2.2
anhyd CH2Cl2, open air
anhyd CH2Cl2, N2
40
40
20
15
15
15
73
65
72
93
92
96
CH2Cl2, H2O (1.0 equiv), N2
CH2Cl2, H2O (2.0 equiv), N2
CH2Cl2, H2O (2.0 equiv), open air
CH2Cl2, H2O (2.0 equiv), open air
In recent years, Dess–Martin periodinane [DMP, 1,1,1-
tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one]
has emerged as the reagent of choice for the oxidation of
primary and secondary alcohols to aldehydes and ketones,
respectively.3 Its unique oxidizing properties and conve-
nience of use make DMP a common oxidizing reagent
employed in the synthesis of biologically important
natural products. For examples, DMP was used in the key
oxidation steps in the total syntheses of cyclotheonamide
B,4 ( )-deoxypreussomerin A,5 ( )-brevioxime,6
erythromycin B,7 (+)-discodermolide,8 (+)-cephalostatin
7,9 (+)-cephalostatin 12,9 (+)-ritterazine K,9 3-O-gal-
loyl-(2R,3R)-epicatechin-4b,8-[3-O-galloyl-(2R,3R)-epi-
catechin],10 fredericamycin A,11 indolizidine alkaloids
(–)-205A, (–)-207A, and (–)-235B,12 1,19-aza-1,19-des-
oxyavermectin B1a,13 angucytcline antibiotics,14 tricyclic
b-lactam antibiotics,15 and the platelet aggregation-inhib-
iting g-lactam PI-091.16 In this paper, we report a new
approach for the preparation of iminoquinones 1b by re-
action of anilines 1a with DMP in CH2Cl2.
a All reactions were run on a 1.5-mmol scale at r.t.
The DMP oxidation reaction was extended to anilines
with various substituents under the optimal conditions
(Table 2). A variety of functional groups were tolerated
on the aryl residue, ranging from the electron-donating
methoxy (entry 4) to the synthetically fertile halides (en-
tries 6–12). Remarkably, even an ortho-substituted phen-
ylaniline, 14a, afforded the corresponding iminoquinone
14b in 80% yield (entry 14). However, the presence of the
strong electron-withdrawing nitro group completely
retarded the reaction (entry 18). In the case of 2-amino-
thiophenol, the oxidation reaction led to a tricyclic com-
pound 16b in 90% yield with the formation of a S–S bond
(entry 16). In another particular case, oxidation reaction of
1,4-phenylenediamine (17a) gave 4,4¢-diazenediylbis-
aniline (17b), but only in the absence of water (entry 17).
The reaction conditions were optimized by examining the
oxidation of 4-methylaniline with DMP under various
In principle, two regioisomeric products could be formed
from the coupling of the aniline 1 to the oxidized quinone.
It was difficult to ascertain which regioisomer was formed
just by 1H and 13C NMR spectroscopy. Unfortunately, we
were unable to isolate any crystals suitable for X-ray
crystal structure analysis. However, it was found that
SYNLETT 2007, No. 11, pp 1679–1682
0
3
.0
7
.2
0
0
7
Advanced online publication: 25.06.2007
DOI: 10.1055/s-2007-984516; Art ID: W24806ST
© Georg Thieme Verlag Stuttgart · New York

1680
H. C. Ma, X. Z. Jiang
LETTER
addition of tetrabutylammonium bromide as an additive in
the reaction of 7a led to the formation of the correspond-
ing bromination product 7c that could be subjected to
X-ray crystallography diffraction analysis (Scheme 1),17
and thus the product regiochemistry was determined.
In brief, we have conducted a synthetic investigation on
the oxidation of anilines via DMP in metal-free systems
and developed a facile protocol for the synthesis of imino-
quinones. As a result of its mildness and good functional
group compatibility, this method might find application in
the synthesis of polycyclic targets and natural products
consisting of iminoquinone moieties. The possible
mechanism is still under investigation and extension of
this preliminary work is now under way in our laboratory.
Scheme 1 Preparation and X-ray crystal structure of 7c
Table 2 Oxidation of Anilines with DMP18
Entry
1
Substratea
Time (min)
10
Product
1b
Yield (%)b
96
N
NH2
NH2
O
1a
2
3
10
15
89
87
NH2
N
N
NH2
O
2a
3a
2b
NH2
NH2
O
3b
4
5
6
15
15
10
79
94
93
N
NH2
NH2
O
O
O
O
4a
4b
N
NH2
NH2
O
5b
5a
6a
Cl
NH2
N
NH2
Cl
Cl
O
6b19
7
8
10
25
85
88
N
NH2
NH2
O
Cl
Cl
Cl
7b
7a
Br
NH2
Br
N
NH2
O
Br
8a
8b
Synlett 2007, No. 11, 1679–1682 © Thieme Stuttgart · New York

LETTER
Novel Synthesis of 2-Amino-1,4-benzoquinone-4-phenylimides
1681
Table 2 Oxidation of Anilines with DMP18 (continued)
Entry
9
Substratea
Time (min)
25
Product
Yield (%)b
84
N
NH2
NH2
O
Br
Br
Br
9a
9b
10
11
25
20
86
81
NH2
N
I
NH2
I
O
I
10a
10b
I
NH2
N
NH2
I
I
O
11a
11b
12
13
14
30
25
25
79
77
80
N
F
NH2
NH2
O
F
F
12b
12a
N
NH2
NH2
Ph
Ph
O
13a
13b
Ph
NH2
N
NH2
O
Ph
14a
15a
14b
15
30
86
NH2
O
NH2
N
15b
16
30
90
84
NH2
NH2
S
S
O
SH
N
16a
16b
17c
18
40
NH2
H2N
N
N
NH2
H2N
17b
17a
overnight
none
NH2
NO2
18a
a Substrates 13a and 14a were prepared according to ref. 20. Others were commercially available and used without further purification.
Reactions were run on a 1.5-mmol scale using DMP (2.2 equiv) and H2O (2.0 equiv) in CH2Cl2 (8 mL) at r.t.
b Isolated yield after column chromatography.
c The reaction was run without H2O.
Acknowledgment
References and Notes
We are grateful to the financial support of the National Natural Sci-
ence Foundation of China (No. 20376071). We are especially gra-
teful to Dr. Mark McCairn (Manchester University) for critical
evaluation of this manuscript.
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Synlett 2007, No. 11, 1679–1682 © Thieme Stuttgart · New York

1682
H. C. Ma, X. Z. Jiang
LETTER
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Hz, 1 H), 6.76–6.82 (m, 2 H), 6.44 (d, J = 6.3 Hz, 1 H), 5.10
(s, 2 H). 13C NMR (100 MHz, CDCl3): d = 180.95, 153.72,
146.74, 140.81, 129.89, 129.49, 129.04, 126.93, 126.02,
124.77, 121.48, 111.99. MS (FAB): m/z = 266.8 [M + H+].
Anal. Calcd for C12H8Cl2N2O: C, 53.96; H, 3.02; N, 10.49.
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Synlett 2007, No. 11, 1679–1682 © Thieme Stuttgart · New York

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