Metal-free, air-promoted, radical-mediated arylation of benzoquinone with phenylhydrazines

Article abstract of DOI:10.1515/znb-2018-0081

An efficient, economic, and air-promoted metal-free method for direct arylation of benzoquinone with phenylhydrazines was developed. This approach leads to the formation of corresponding [1,1′-biphenyl]-2,5-dione derivatives as biological and pharmaceutic

Full text of DOI:10.1515/znb-2018-0081

Z. Naturforsch. 2018; aop
Mohammad Hosein Sayahi, Samira Ansari, Seyyed Jafar Saghanezhad*
aMndeMtoahalm-mfraed Mea,hdaaivir*-promoted, radical-mediated
arylation of benzoquinone with phenylhydrazines
https://doi.org/10.1515/znb-2018-0081
employing aryl halides for Stille and Heck type coupling
reactions have their own drawbacks, as they require
using pre-functionalized quinones and aryl sources,
respectively [12, 13].
Therefore, taking benefit of direct C–H arylation
methods using simple arenes is highly advantageous,
as they are dependent on using functionalized starting
materials. In 1985, Itahara reported an oxidative coupling
of quinones with simple arenes in the presence of sto-
chiometric and catalytic amounts of Pd(OAc)2 and Na2S2O8
Received April 29, 2018; accepted August 10, 2018
Abstract: An efficient, economic, and air-promoted metal-
free method for direct arylation of benzoquinone with
phenylhydrazines was developed. This approach leads to
the formation of corresponding [1,1′-biphenyl]-2,5-dione
derivatives as biological and pharmaceutical materials of
interest in good yields, under mild reaction conditions,
and at ambient temperature.
Keywords: [1,1′-biphenyl]-2,5-dione; benzoquinone; cross- as the reoxidant [14]. In 2013, You and co-workers devel-
coupling reaction; direct arylation; phenylhydrazine.
oped a Pd(acac)2-catalyzed approach to aryl quinones
from hydroquinones using Ag2CO3 as the oxidant [15]. In
2014, the same group reported another protocol for the
arylation of quinones as well as olefins using Pd(TFA)2
with (NH4)2S2O8 [16]. The aforementioned reports suffer
from the common problem of direct arylation reactions
with simple arenes and lack of regioselectivity in the
corresponding products. In 2015, Hong and co-workers
reported a Rh-catalyzed direct coupling of quinones and
benzamide derivatives to overcome the regioselectivity
problem by using a directing group [17].
Arylboronic acids are another important and available
class of arylating agents used in several reports. In 2009,
Molina et al. introduced a synthetic pathway for arylation
of benzo-fused 1,4-quinones by the addition of arylboronic
acids in the presence of Pd/Cu as the catalyst and FeCl3 as
the co-oxidant [18]. From then onwards, different transi-
tion metal salts such as AgNO3 [19], FeS [20], FeNO3 [21],
Fe(acac)2 [22], and FeSO4 [23] were used as catalysts in com-
bination with excess amounts of K2S2O8 as the oxidant. In
2014, Lee and co-workers reported diarylation of quinones
using arylboronic acids catalyzed by (Pd(OCOCF3)2 [24]. In
2015, Ilangovan et al. developed a metal-free K2S2O8-medi-
ated arylation of quinones with arylboronic acids [25]. In
the same year, Ding and co-workers reported an Ir-cata-
lyzed arylation of quinones under room temperature [26].
All the previous reports [4, 27–29] include impor-
tant drawbacks such as using transition metal catalysts,
employing heat, scarce availability of Ar2IOTf salts, or
using harmful starting materials such as o-iodoxyben-
zoic acid. These shortcomings make these approaches
less attractive because of the presence of metal toxicity,
1 Introduction
The quinone moiety is a ubiquitous skeletal framework
found in several natural products and biologically active
compounds [1–4]. Among such various substituted struc-
tures bearing a quinone subunit, arylated quinones were
found to have chemotherapeutic value as well as anti-
biotic, antiviral, antitumor, antimalarial, and antidiabetic
effects [5–8]. Furthermore, from the unique electronic and
visual properties of arylated quinones have emerged their
usage in the dye industry and in photosynthesis, as photo-
active materials [9, 10].
During recent years, tremendous progress was
made in the area of synthesizing arylated quinones,
using different aryl counter parts. Since 1961, Bagli
and L’Ecuyer [11] reported Meerwein arylation of qui-
nones, and several procedures were developed for the
same purpose which would be mentioned as follows:
*Corresponding authors: Seyyed Jafar Saghanezhad, ACECR –
Production Technology Research Institute, Ahvaz, I. R. Iran,
e-mail: saghanezhad@acecr.ac.ir; and Mohammad Mahdavi,
Endocrinology and Metabolism Research Center, Endocrinology and
Metabolism Clinical Sciences Institute, Tehran University of Medical
Sciences, Tehran, I. R. Iran, e-mail: mahdavi_chem@yahoo.com
Mohammad Hosein Sayahi: Department of Chemistry, Payame Noor
University (PNU), PO Box 19395-3697, Tehran, I. R. Iran
Samira Ansari: CinnaGen Medical Biotechnology Research Center,
Alborz University of Medical Sciences, Karaj, I. R. Iran
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ꢀꢀꢀꢁ
2ꢀ ꢀM.H. Sayahi et al.: Metal-free, air-promoted, radical-mediated arylation of benzoquinone
environmental pollution, and uneconomical procedures. Among the tested solvents, dimethyl sulfoxide (DMSO)
Therefore, the development of an efficient, convenient, showed high productivity.
economical, and practical protocol for direct arylation of
With the optimized reaction conditions identified,
quinones was desired. Herein, we would like to report an to ensure the efficiency of the present method for direct
air-promoted direct and selective arylation of 1,4-benzo- metal-free arylation of benzoquinone, the scope of various
quinone with phenylhydrazine derivatives in the presence phenylhydrazines was investigated as summarized in
of K2CO3 at an ambient temperature.
Table 2. Different electron-donating and electron-with-
drawing substituents such as Me, OMe, halogens, NO2,
and CN on the aryl ring of phenylhydrazine were all well
tolerated and the corresponding products were achieved
with good yields (3a–h).
While DMA, NMP, and MeOH led into a drastic drop
in the reaction yield (entries 7–10) as expected, the reac-
tion progress was suppressed in the absence of O2 due
to its vital role in the aryl radical formation (entry 11).
Notably, no desired products were formed in the absence
2 Results and discussion
Our studies began with the optimization of the reaction
conditions between 1,4-benzoquinone (1) and phenylhy-
drazine (2a) as the model substrates. The effects of dif-
ferent bases, solvents, and reaction atmosphere on the
reaction progress were monitored and the results are sum-
marized in Table 1. We began our study with Na2CO3 as
the base, which gave the desired product 3a in 31% yield
(entry 1). Examining other carbonate bases like Ag2CO3,
K2CO3, and Cs2CO3, the obtained results revealed the essen-
tial role of a base in this reaction progress. With K2CO3 the
yield increased to 80%, while other carbonate bases were
not effective enough (entries 2–4). Using NaOEt and KOtBu
also resulted in a decrease of the reaction yield to 51%
and 26%, respectively (entries 5 and 6). In the next step,
we examined different solvents with K2CO3 as the base.
Table 2:ꢀSynthesis of [1,1′-biphenyl]-2,5-dione derivatives.a
Table 1:ꢀOptimization of the reaction conditions.
Entryꢁ
Base
ꢁ
Solventꢁ
Yield (%)a
1
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
Na2CO3ꢂ
Ag2CO3 ꢂ
DMSO ꢂ
DMSO ꢂ
DMSO ꢂ
DMSO ꢂ
DMSO ꢂ
DMSO ꢂ
31
36
80
53
51
26
38
24
23
45
30
0
2
3
K2CO3
ꢂ
ꢂ
4
Cs2O3
5
NaOEt ꢂ
6
KOtBu ꢂ
7
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
–
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
DMF
DMA
NMP
ꢂ
ꢂ
ꢂ
8
9
10
11b
12
MeOH ꢂ
DMSO ꢂ
DMSO ꢂ
Reaction conditions: 1,4-Benzoquinone (1.0 mmol), phenylhydrazine
(1.2 mmol), base (3.0 mmol), solvent (15 mL), air, r. t., 12 h. aIsolated
yields. bUnder atmosphere of N2. The optimized entry has been
shown in bold text.
aReaction conditions: all reactions were performed with
1,4-benzoquinone (1.0 mmol), phenylhydrazine derivative
(1.2 mmol), K2CO3 (3.0 mmol), DMSO (15 mL), air, r. t., 12 h.
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ꢃ3
M.H. Sayahi et al.: Metal-free, air-promoted, radical-mediated arylation of benzoquinoneꢃ
4 Experimental section
4.1 General remarks
All chemicals were purchased from Merck and Fluka
1
companies. All yields refer to isolated products. H NMR
and 13C NMR spectra were recorded using a Brucker,
Rheinstetten, Germany NMR spectrometer (at 500 MHz)
using tetramethylsilane as the internal standard. The
progress of the reaction was followed with thin layer
chromatography using silica gel SILG/UV 254 and 365
plates. All products are known compounds and their
structures were deduced using 1H NMR and 13C NMR spec-
troscopies. These data and further numbers pertinent to
the characterization of the products are given as support-
ing information available online.
Fig. 1:ꢀExamples of [1,1′-biphenyl]-2,5-dione derivatives with
biological and medicinal activities.
4.2 General procedure for the preparation
of [1,1′-biphenyl]-2,5-dione (3a–h)
A solution of 1,4-benzoquinone (1.0 equiv.), phenylhydra-
zine derivative (1.2 equiv.), and potassium carbonate
(3.0 equiv.) in DMSO (15 mL) was stirred at room tempera-
ture for 12 h. After completion of the reaction, the reaction
Scheme 1:ꢀPlausible reaction mechanism.
of K2CO3 as the base (entry 12). It was clearly concluded mixture was diluted with water (80 mL) and the aqueous
that the best results were achieved with three equivalents layer was extracted with ethyl acetate (3ꢀ×ꢀ20 mL). The
of K2CO3 in DMSO, under air at room temperature (entry 3) organic layer was further dried over Na2SO4 (anhydrous)
(Fig. 1).
and evaporated in vacuo. Purification was performed by
A plausible mechanism for this air-promoted reaction column chromatography using [hexane:ethyl acetate (3:1)]
is shown in Scheme 1.
to obtain the desired products.
First, arylhydrazine (2) is oxidized by air (O2) to form
arylhydrazyl radical (4), followed by release of N2 to yield
aryl radical (5), which is then added to 1,4-benzoquinone 4.2.1 2′,5′-dioxo-2′,5′-dihydro-[1,1′-biphenyl]-
(1) to produce radical (6), and [1,1′-biphenyl]-2,5-dione
derivatives (3a–h) would be formed after rearomatization
of 6.
4-carbonitrile (3h)
Yellow solid, m.p.: 142–144°C. – 1H NMR (500 MHz, CDCl3):
δꢀ=ꢀ7.48 (d, Jꢀ=ꢀ8.8 Hz, 2H), 6.97 (d, Jꢀ=ꢀ8.8 Hz, 2H), 6.86–6.79
13
(m, 3H). – C NMR (125 MHz, CDCl3): δꢀ=ꢀ187.7, 187.1, 161.4,
145.2, 137.0, 136.3, 131.1, 130.9, 125.0, 118.2, 114.2. – CHN
Analysis for C13H7NO2:calcd. C 74.64, H 3.37, N 6.70; found
C 74.81, H 3.46, N 6.55. – HRMS [(+)-ESI]: m/zꢀ=ꢀ209.0483
3 Conclusion
In conclusion, an efficient air-promoted method for
the synthesis of [1,1′-biphenyl]-2,5-diones was devel-
oped from the coupling of various arylhydrazines and
1,4-benzoquinone. The reaction proceeds under mild
+
(calcd.) 209.0476 for C13H7NO2, [M] .
reaction conditions at ambient temperature to afford 5 Supporting information
the desired products in good yields. This protocol pro-
vides a cost-effective, efficient, facile, and convenient 1H and 13C NMR spectral data of 3a–h as well as copies of
method for the preparation of [1,1′-biphenyl]-2,5-dione these spectra are given as supplementary material avail-
derivatives.
able online (DOI: 10.1515/znb-2018-0081).
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Z. Naturforsch.ꢃ
ꢃ2018 | Volume x | Issue x(b)
Graphical synopsis
R
Mohammad Hosein Sayahi, Samira Ansari,
Seyyed Jafar Saghanezhad and Mohammad
Mahdavi
Metal-free, air-promoted, radical-
mediated arylation of benzoquinone
with phenylhydrazines
O
O
O
K2CO3
DMSO, r. t.
R
H
H2NHN
O
https://doi.org/10.1515/znb-2018-0081
Z. Naturforsch. 2018; x(x)b: xxx–xxx
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