Spectroscopic and structural aspects of the reactions of 1,4-quinones with sulfur and nitrogen nucleophiles

Article abstract of DOI:10.1016/j.crci.2013.10.022

A series of 1,4-benzoquinone derivatives from 2,5-dichloro-3,6-diethoxy-1, 4-benzoquinone and 2,6-dichloro-3,5-diethoxy-1,4-benzoquinone were prepared by nucleophilic substitution reactions of sulfur and nitrogen nucleophiles. Spectral techniques (¹H NMR, ¹³C NMR, FT-IR, and LC-MS) were employed to structurally characterize the reaction products of alkoxy, chloro substituted-1,4-benzoquinones with thiols and amines in the presence of sodium carbonate in ethanol at room temperature. The orientations and the regioselectivity of the reactions of alkoxy, chloro substituted-1,4- benzoquinones with various thiol and amine nucleophiles are discussed.

Full text of DOI:10.1016/j.crci.2013.10.022

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Contents lists available at ScienceDirect
Comptes Rendus Chimie
www.sciencedirect.com
´
Full paper/Memoire
Spectroscopic and structural aspects of the reactions
of 1,4-quinones with sulfur and nitrogen nucleophiles
b
a
a
Nilufer Bayrak a, , Amac¸ Fatih Tuyun , Hatice Yıldırım , Nihal Onul
*
a Istanbul University, Faculty of Engineering, Department of Chemistry, Istanbul, Turkey
b Beykent University, Faculty of Engineering and Architecture, Department of Chemical Engineering, Istanbul, Turkey
A R T I C L E I N F O
A B S T R A C T
Article history:
A series of 1,4-benzoquinone derivatives from 2,5-dichloro-3,6-diethoxy-1,4-benzoqui-
none and 2,6-dichloro-3,5-diethoxy-1,4-benzoquinone were prepared by nucleophilic
substitution reactions of sulfur and nitrogen nucleophiles. Spectral techniques (1H NMR,
13C NMR, FT–IR, and LC–MS) were employed to structurally characterize the reaction
products of alkoxy, chloro substituted-1,4-benzoquinones with thiols and amines in the
presence of sodium carbonate in ethanol at room temperature. The orientations and the
regioselectivity of the reactions of alkoxy, chloro substituted-1,4-benzoquinones with
various thiol and amine nucleophiles are discussed.
Received 21 July 2013
Accepted after revision 29 October 2013
Available online xxx
Keywords:
Substituted 1,4-quinones
Thiols
Amines
´
ß 2013 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Nucleophiles
Chloranil
1. Introduction
recent years, the concept of privileged medicinal structures or
scaffolds that commonly consist of quinone moiety, which
Quinones are prevalent structural components in
various natural products, which are associated with diverse
biological activities, including antibacterial, antimalarial,
antifungal, antitumor activities [1–5]. The biological activity
of the quinones originates from the redox chemistry of the
quinone system [6]. A great deal of research has been
conducted in recent years on the charge transfer complexes of
quinones because of their wide applications ranging from
chemistry, medicine to biology [7,8]. Despite the fact that
natural products are important sources of new biologically
active molecules for drug discovery, their structural complex-
ity and poor availability make greatly difficult natural
product-based drug discovery. The discovery of new syn-
thetic methodologies for the preparation of organic com-
pounds is aprimefocus of the researches in the field of current
organic, bioorganic, and medicinal chemistry [9–12]. In
contains heteroatoms as substituents, has emerged as one of
the guiding principles of drug discovery process [3,13].
Quinone derivatives have been widely investigated for cancer
therapy and many drugs containing aquinone moiety, such as
anthracyclines, daunorubicin, mitomycin, and saintopin have
received clinical approval for cancer treatment [13–16].
Structure–activity relationship of quinone compounds
showed that the ring number, the position, and number of
heteroatoms in the side chain or inside the ring with
various substituents are very crucial to affect the biological
activities [17]. Especially, we have known incorporation of
a heteroatom such as a sulfur or nitrogen atom into the ring
of the quinone skeleton can change the physicochemical
properties and create a new pharmacophore with a
different biological profile [17]. Chemical structures of
biologically important compounds that include the ben-
zoquinone core and sulfur or nitrogen atoms in the side
chain or inside the ring with various substituents are
shown in Fig. 1 [1,3,11,18–20]. The interesting biological
profile resulting from the presence of a heteroatom, sulfur
*
Corresponding author.
E-mail address: niluferbayrak@gmail.com (N. Bayrak).
1631-0748/$ – see front matter ß 2013 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.crci.2013.10.022
Please cite this article in press as: Bayrak N, et al. Spectroscopic and structural aspects of the reactions of 1,4-quinones
with sulfur and nitrogen nucleophiles. C. R. Chimie (2014), http://dx.doi.org/10.1016/j.crci.2013.10.022

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Biological
properties
Biological
properties
Compounds
Compounds
Antifungal
activity
Antimalarial
activity
R/Ar: C6H5, CH3-C6H5,…
Calothrixin A
Calothrixin B
Antifungal
and
antibacterial
activity
Antimalarial
activity
Antifungal
activity
Urease
inhibitors
R = C4H10, C4H8
R1, R2, R3, R4 = H, Me,..
Antibacterial
and
antitumour
activity
Anti-breast
cancer
activity
R1, R2 = H, CH3, CH3O..
R1 = Br, Cl,.. R2 = Br, Cl,..
R3 = CH3, C6H5,.. R6 = H
R7 = CH3O
Fig. 1. Chemical structures of biologically active 1,4-benzoquinones.
or nitrogen, prompted us to synthesize quinone derivatives
possessing nitrogen and sulfur atoms.
We aimed to synthesize new 1,4-benzoquinone com-
pounds, which not only may give promising candidates
with respect to biological activity but also may be potent
receptors for interaction with drugs. Although there were a
lot of studies investigating features and reactions of
quinones, there is a notable lack of information about
the structural aspects on the nucleophilic substitution
reactions of 1,4-quinone derivatives. Additionally, we have
focused on nucleophilic reactions of 1,4-quinones and
spectroscopic, structural aspects of the reactions of
quinones with sulfur and nitrogen nucleophiles. We also
observed the behavior of the two isomers of alkoxy, chloro
substituted-1,4-benzoquinones on nucleophilic reactions.
There have been new studies about charge transfer
complexes of a number of quinones with a variety of
donors [21–23] and the mechanism behind the interaction
of quinone with drugs. In recent years, the spectral,
thermodynamic, and kinetic aspects of the interaction of
1,4-benzoquinones with variable alkyl chain of alkoxy
groups such as 2,3,5-trichloro-6-methoxycyclohexa-2,5-
diene-1,4-dione, 2,3,5-trichloro-6-ethoxycyclohexa-2,5-
diene-1,4-dione, and 2,3,5-trichloro-6-butoxycyclohexa-
2,5-diene-1,4-dione with sulfamethoxazole drug were
investigated for understanding the mechanism of the
interaction and to characterize the structures of the
products formed in these interactions [24].
2. Results and discussion
The reactivity of quinones towards nucleophiles is
dependent to a large degree on the
and electron affinity of the quinones. To the best of our
knowledge, LCAO-MO calculations for 1,4-benzoquinone
p
-acceptor character
1,4-Benzoquinones are known to be easily reacted with
various nucleophiles in different conditions [29,30]. Earlier
studies show that when chloranil (1) reacts with thiol in
the presence of Na2CO3 and ethanol, alcohol can act as a
nucleophile along with thiol, and replace chloro atoms
[31]. We have observed this situation in the reaction of
chloranil (1) with n-octylthiol in the presence of Na2CO3
and ethanol (Scheme 1).
In the beginning of our studies, we studied the chloranil
compound to obtain new quinone derivatives but due to
high reactivity of chlorine atoms in the structure, a lot of
by-products were obtained. This situation suffers from the
low yields and serious difficulties in purification. We
decided to assist p-chloranil by two ethoxy groups to
have shown that the distribution of
p-electron density is
very changeable. This class of compounds has a diverse
range of activities because of a wide variation in the
electron density of quinones [25]. Possible variations in
substitution models on the quinone ring affect its
capability to accept electrons and so its capacity to
reconcile biological reactions [26,27]. As shown in Fig. 2,
electron affinity can be increased by appropriate substitu-
tion of the quinone. The electron affinity of unsubstituted
1,4-benzoquinone, which has a low value (1.91 eV), can be
changed by replacement of hydrogen by other atoms [28].
Please cite this article in press as: Bayrak N, et al. Spectroscopic and structural aspects of the reactions of 1,4-quinones
with sulfur and nitrogen nucleophiles. C. R. Chimie (2014), http://dx.doi.org/10.1016/j.crci.2013.10.022

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3
Electron
Compounds
affinity
Electron
affinity
Compounds
1.91 eV
1.59 eV
Duroquinone
p-Benzoquinone
Chloranil
2.78 eV
3.40 eV
Tetracyanoquinone
2.50 eV
Bromanil
Fig. 2. Electron affinity of 1,4-benzoquinones.
Scheme 1.
enhance the regioselectivity towards nucleophiles in order
to overcome these problems. In light of such reactions, we
decided to synthesize 2,5-dichloro-3,6-diethoxy-1,4-ben-
zoquinone and 2,6-dichloro-3,5-diethoxy-1,4-benzoqui-
none separately. Investigations concerning how these
isomers act towards the different nucleophiles and what
structural aspects of the reactions of these compounds were
made. Firstly, we synthesized starting materials namely 2,5-
dichloro-3,6-diethoxy-1,4-benzoquinone (3) and 2,6-
dichloro-3,5-diethoxy-1,4-benzoquinone (4) prepared from
chloranil(1)withethanolinthepresenceoftriethylamineas
indicated in the literature [32] (Scheme 2).
The ethoxy, chloro substituted-1,4-benzoquinones (3,
4) with various thiol and amine nucleophiles (Schemes 3
and 4) gave 5–13 products by nucleophilic substitution
reactions. The reactions have been performed with
different sulfur and nitrogen nucleophiles in ethanol or
CHCl3, in the presence of a base.
so one chlorine atom exchanged by nucleophile. In this
reaction, it has also been determined that the initially
formed monoadduct 5 may undergo further nucleophilic
addition to give disubstituted adduct 6 resulting in a
regioselectivity for the 5 position that contains second
chlorine atom. In the reaction of 3 with thiomorpholine,
most probably, nucleophile attended firstly in 2 position to
give monoadducts and this compound may undergo
nucleophilic addition to give trisubstituted adduct 7.
In the 1H NMR spectra, compounds 5 and 6 exhibited
the methyl protons of thiol groups in the range 1.18–
1.22 ppm and methyl protons of ethoxy groups at 1.31–
1.36 as triplet. While the –SCH2 protons were observed at
2.99–3.09 ppm, the –OCH2 protons were observed around
4.22–4.29 ppm as quartet. 13C spectra of the 5 showed two
carbon signals at 174.58 and 176.99 ppm for carbonyl
groups, compound 6 gave only one carbon signal at
175.44 ppm due to the symmetry of the molecule. Mass
spectra of 5 and 6 confirmed the proposed structure. The
molecular ion peak [M]+ was identified at m/z 290.14 with
strong abundance (100%) for 5 and at m/z 316.33 for 6.
In the reaction of 3 with ethanethiol, the compounds 5
and 6 were obtained in a one-pot fashion. While in the
forming compound 5, nucleophile chose to attend 2 position
Scheme 2.
Please cite this article in press as: Bayrak N, et al. Spectroscopic and structural aspects of the reactions of 1,4-quinones
with sulfur and nitrogen nucleophiles. C. R. Chimie (2014), http://dx.doi.org/10.1016/j.crci.2013.10.022

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O
O
SH
Cl
O
S
S
O
S
+
Na2CO3/EtOH
O
O
O
O
5
O
6
Cl
O
4
5
3
2
6
1
O
O
3
Cl
S
O
S
S
S
N
N
N
NH
Na2CO3/EtOH
Cl
O
7
Scheme 3.
Scheme 4.
In the reaction of 4, which is the isomer structure of 3
with hexadecanethiol, compound 8 was obtained by the
nucleophilic substitution reaction in the 2 position. It was
also observed that the nucleophile replaced the chlorine
atom in 2 position, like in the formation of the 5 structure.
The reaction of 4 with morpholine gave three products 9,
10, and 11 that is a known compound [33]. We defined by
the construction of 9 that nucleophile preferred one
chlorine atom in 2 position and ethoxy group in 5
position. 9 may undergo nucleophilic addition to give
trisubstituted adduct 10 and tetrasubstituted adduct 11
[33]. It was determined in the structure of 12 that the
nucleophile substituted two chlorine atoms. In the
formation of 13, it was seen that the nucleophile chose
one chlorine atom in 2 position and an ethoxy group in 5
position.
0.80–0.82 as triplet and methyl protons of ethoxy groups at
1.16–1.24 as multiplet. While the –SCH2 protons were
observed at 3.01–3.04 ppm, the methylene protons of
ethoxy group were observed around 4.21–4.43 ppm as
quartet. 13C spectra of the 8 showed two carbon signals at
174.58, 176.97 ppm for carbonyl groups. In the mass
spectra of 8 the molecular ion peak [M]+ was identified at
m/z 486.75 with strong abundance (100%) for 8.
9 gave methyl protons of ethoxy groups at 1.27–
1.30 ppm as multiplet, –NCH2 protons of morpholine ring
at 3.40–3.51 ppm, –OCH2 protons of morpholine ring at
3.71–3.76 ppm and methylene protons of ethoxy groups at
3.84–3.88 ppm in the 1H NMR spectra. In the compound
10, while –NCH2 protons of morpholine ring at 3.05–
3.48 ppm, –OCH2 protons of morpholine ring at 3.66–
3.75 ppm. Carbonyl groups in the 13C spectra showed two
carbon signals at 178.41 and 216.2 ppm for 9, and 178.73
and 180.77 ppm for 10.
In the 1H NMR spectra of 8, the methyl protons of thiol
groups have shown typical ppm values within the range
Please cite this article in press as: Bayrak N, et al. Spectroscopic and structural aspects of the reactions of 1,4-quinones
with sulfur and nitrogen nucleophiles. C. R. Chimie (2014), http://dx.doi.org/10.1016/j.crci.2013.10.022

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5
Compounds 12 gave methyl protons of ethoxy groups at
1.25–1.28 ppm as triplet, –CH2 protons of ethoxy groups at
4.16–4.21 ppm as multiplet, 5CH–proton at 6.04–
6.19 ppm as doublet, O5CH proton at 7.22–7.23 as
doublet. 13C spectra of the 12 showed two carbon signals
at 174.41 and 180.51 ppm for carbonyl groups.
In the 1H NMR spectra of 13, methyl protons of ethoxy
groups at 0.68–0.94 as multiplet. The –CH2 protons of
ethoxy groups were observed around 3.95–4.06 ppm as
multiplet and aromatic protons of phenyl ring at 6.91–7.30
as multiplet. 13C spectra of the 13 showed two carbon
signals at 174.16 and 178.72 ppm for carbonyl groups. The
molecular ion peak [M + Na]+ was identified at m/z 425.0
with strong abundance (100%) for 13.
4.1. General procedure for the synthesis of new derivatives of
1,4-benzoquinones
Sodium carbonate (1.52 g) was dissolved in ethanol or
chloroform (68.75 mL) and into the resulting solution,
firstly ethoxy, chloro 1,4-benzoquinone and then thiol/
amine were added in small portions at room temperature.
The mixture was stirred until completion of the reaction
(TLC). The residue was extracted with chloroform. The
organic layer was separated and washed with water
(4 Â 30 mL), and dried with Na2SO4. The solvent was
evaporated and the residue was purified by column
chromatography on silica gel.
4.1.1. 2,5-diethoxy-3,6-bis(octylthio)cyclohexa-2,5-diene-
1,4-dione (2)
3. Conclusions
Compound 2 was synthesized by the reaction of 1.845 g
(7.5 mmol) p-chloranil (1) with 4.39 g (30 mmol) octa-
nethiol.
There can be no doubt that the quinone compounds
deserve the great prominence by exhibiting a broad
spectrum of biological activities and forming the charge
transfer complexes that have enormous applications
ranging from sensors, magnetic materials to chemistry
of drugs. Even if conjugate addition reaction of p-quinones
is well studied, many aspects regarding the regioselectivity
observed in the reaction of substituted quinones still
remain obscure. In the context of our ongoing interest to
prepare new derivatives of quinones by nucleophilic
substitution and characterize these compounds, differ-
ences in regioselectivity were observed. It can be
concluded that nucleophiles choose chlorine atoms to
replace in the 2 position both isomer structures in the
formation of monoadducts 5 and 8 with thiol nucleophiles,
whereas nucleophiles usually prefer 5 position for second
substitution in the formation of bis adducts 2, 6, and 9. The
2: yield 0.54 g (15%); brown oil; IR (Film)
(CHaliphatic), 1680 (C5O), 1475 (C5C) cmÀ1 1H NMR
(499.74 MHz, CDCl3) 0.85–0.89 (m, 6H, 2CH3CH2S–),
n 2988
;
d
1.23–1.67 (m, 30H, 12CH2; 6H, 2CH3CH2O–), 2.61–3.06 (m,
4H, 2CH3CH2S–), 4.12–4.37 (m, 4H, 2CH3CH2O–); 13C NMR
(125 MHz, CDCl3)
d 13.86, 14.27, 26.72, 69.48, 124.65,
129.40, 154.36, 178.54; MS m/z (%): 486.3 (M+), C26H44O4S2
(M, 484.77); anal. calcd. for C26H44O4S2: C 64.42, H 9.15;
found: C, 64.11, H 9.18.
4.1.2. 2-Chloro-3,6-diethoxy-5-(ethylthio)cyclohexa-2,5-
diene-1,4-dione (5) and 2,5-diethoxy-3,6-
bis(ethylthio)cyclohexa-2,5-diene-1,4-dione (6)
Compounds 5 and 6 were synthesized by the reaction of
0.150 g (0.57 mmol) 2,5-dichloro-3,6-diethoxy-1,4-benzo-
quinone (3) with 0.035 g (0.57 mmol) ethanethiol.
trisubstituted products
7 and 10 were obtained by
substitution in 2, 3, and 5 position and nucleophile
preferred the ethoxy groups for third substitution in both
isomers. In conclusion, we have synthesized a series of new
1,4-benzoquinone derivatives that are the promising
candidates with respect to biological activity and as new
receptors for drugs.
5: yield 0.041 g (25%); brown oil; IR (Film)
(CHaliphatic), 1650 (C5O), 1500 (C5C) cmÀ1 1H NMR
(499.74 MHz, CDCl3) 1.19–1.22 (t, J = 7.32, 3H, 1CH3CH2S–
n 2945
;
d
), 1.32–1.36 (t, J = 6.83, 6H, 2CH3CH2O–), 3.05–3.09 (q, J = 7.32,
2H, 1CH3CH2S–), 4.22–4.26 (q, J = 6.83, 2H, 1CH3CH2O–),
4.38–4.43 (q, J = 7.32, 2H, 1CH3CH2O–); 13C NMR (125 MHz,
CDCl3)
d 14.18, 14.70, 14.86, 26.60, 69.03, 69.50, 124.87,
4. Experimental
130.60, 152.25, 153.07, 174.58, 176.99; MS m/z (%): 290.14
(M+), C12H15ClO4S (M, 290.76); anal. calcd. for C12H15ClO4S: C
49.57, H 5.20; found: C, 49.51 H 5.16.
6: yield 0.088 g (40%); dark brown oil; IR (Film)
(CHaliphatic), 1645 (C5O), 1489 (C5C) cmÀ1 1H NMR
(499.74 MHz, CDCl3) 1.18–1.21 (t, J = 7.32, 6H,
2CH3CH2S–), 1.31–1.34 (t, J = 7.32, 2CH3CH2O–), 2.99–
3.04 (q, J = 7.32, 4H, 2CH3CH2S–), 4.23–4.30 (q, J = 6.83, 4H,
2CH3CH2O–); 13C NMR (125 MHz, CDCl3)
All chemicals were reagent grade and used without
further purification. Progress of the reactions and purity of
compounds were monitored by thin layer chromatography
(TLC), which was performed on Merck silica gel plates
(60F254), and compounds were detected with ultraviolet
light (254 nm). Products were isolated by column chro-
matography on silica gel (Fluka silica gel 60, particle size
n 2973
;
d
d 15.42, 15.98,
63–200 mm). Melting points were measured on a Buchi B-
540 melting point apparatus and are uncorrected. 1H NMR
(500 MHz) and 13C NMR (125 MHz) spectra were recorded
in CDCl3 on a Varian UNITY INOVA spectrometer. Infrared
(IR) spectra were recorded on a Thermo Scientific Nicolet
6700 spectrometer. Microanalyses were performed on a
Carlo Erba 1106 elemental analyzer. Mass spectra were
obtained on a Thermo Finnigan LCQ Advantage MAX LC/
MS/MS spectrometer using ion-trap mass analyzer for
either APCI or ESI source.
27.71, 70.06, 131.84, 154.99, 175.44; MS m/z (%): 316.33
(M+), C14H20O4S2 (M, 316.44); anal. calcd. for C14H20O4S2: C
53.14, H 6.37; found: C 53.32, H 6.20.
4.1.3. 2-Chloro-3,5,6-trithiomorpholinocylohexa-2,5-diene-
1,4-dione (7)
Compound 7 was synthesized by the reaction of 0.10 g
(0.38 mmol) 2,5-dichloro-3,6-diethoxy-1,4-benzoquinone
(3) with 0.078 g (0.76 mmol) thiomorpholine.
Please cite this article in press as: Bayrak N, et al. Spectroscopic and structural aspects of the reactions of 1,4-quinones
with sulfur and nitrogen nucleophiles. C. R. Chimie (2014), http://dx.doi.org/10.1016/j.crci.2013.10.022

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7: yield 0.084 g (50); black oil; IR (Film)
(CHaliphatic), 1655 (C5O), 1493 (C5C) cmÀ1
(499.74 MHz, CDCl3) 2.67–2.69 (t, J = 4.88, 12H, 6CH2S–),
3.51–3.53 (t, J = 4.88, 12H, 6CH2N–); 13C NMR (125 MHz,
CDCl3) 27.12, 52.36, 121.32, 146.84, 172.9, 179.22; anal.
n
2954
4.1.6. 2,6-Bis((furan-2-yl)methylthio)-3,5-
;
1H NMR
diethoxycyclohexa-2,5-diene-1,4-dione (12)
d
Compound 12 was synthesized by the reaction of 0.19 g
(0.71 mmol) 2,6-dichloro-3,5-diethoxy-1,4-benzoquinone
(4) with 0.16 g (1.42 mmol) furanthiol.
d
calcd. for C18H24ClN3O2S3: C 48.47, H 5.42; found: C 48.24
H 5.37.
12: yield 0.11 g (38%); brown oil; IR (Film)
(CHaliphatic), 1656 (C5O), 1549 (C5C) cmÀ1 1H NMR
(499.74 MHz, CDCl3) 1.25–1.28 (t, J = 7.32, 6H,
n 2961
;
d
2CH3CH2O–), 4.16–4.21 (m, 8H; 4H, 2CH3CH2O–, 4H,
2SCH2), 6.04–6.05 (d, J = 2.44, 2H, 5CH–), 6.17–6.19 (t,
J = 2.68, 2H, 5CH–), 7.22–7.23 (d, 2H, O–CH5); 13C NMR
4.1.4. 2-Chloro-3,5-diethoxy-6-(hexadecylthio)cyclohexa-
2,5-diene-1,4-dione (8)
Compound 8 was synthesized by the reaction of 0.180 g
(0.68 mmol) 2,6-dichloro-3,5-diethoxy-1,4-benzoquinone
(4) with 0.176 g (0.68 mmol) hexadecanethiol.
(125 MHz, CDCl3)
d 14.67, 28.82, 69.11, 107.26, 109.53,
128.49, 141.35, 149.88, 154.95, 174.41, 180.51; MS m/z
(%): 443.2 (M + Na+), C20H20O6S2 (M, 420.5); anal. calcd. for
8: yield 0.2 g (60%); brown oil; IR (Film)
(CHaliphatic), 1663 (C5O), 1476 (C5C) cmÀ1
(499.74 MHz, CDCl3) 0.80–0.82 (t, J = 6.83, 3H, 1CH3–),
n
2946
C
20H20O6S2 C 57.13, H 4.79; found: C 57.48, H 4.71.
;
1H NMR
d
4.1.7. 2-Chloro-5-ethoxy-3,6-bis(phenylthio)cyclohexa-2,5-
diene-1,4-dione (13)
Compound 13 was synthesized by the reaction of 0.19 g
(0.71 mmol) 2,6-dichloro-3,5-diethoxy-1,4-benzoquinone
(4) with 0.078 g (0.71 mmol) phenylthiol.
1.16–1.24 (m, 28H, 14CH2–), 1.32–1.36 (t, J = 7.32, 6H,
2CH3CH2O), 3.01–3.04 (t, J = 7.32, 2H, 1CH2S–), 4.21–
4.25 (q, J = 6.83, 2H, 1CH3CH2O–), 4.34–4.43 (q, J = 7.32,
2H, 1CH3CH2O–); 13C NMR (125 MHz, CDCl3)
d 13.10,
14.71, 14.86, 21.68, 27.66, 28.11, 28.35, 28.46, 28.55,
28.64, 28.67, 28.69, 29.12, 30.91, 32.32, 69.00, 69.48,
124.88, 131.10, 152.24, 153.07, 174.58, 176.97; MS m/z
(%): 486.75 (M+), C26H43ClO4S (M, 487.14); anal. calcd.
13: yield 0.041 g (30%); brown oil; IR (Film)
(CHaromatic), 1657 (C5O), 1478 (C5C) cmÀ1 1H NMR
(499.74 MHz, CDCl3) 0.68–0.94 (m, 3H, 1CH3CH2O–),
3.95–4.06 (m, 2H, 1CH3CH2O–), 6.91–7.30 (m, 10H,
2 C6H5–); 13C NMR (125 MHz, CDCl3)
15.28, 46.92,
n 3025
;
d
for C26H43ClO4S:
H 8.87.
C 64.11, H 8.90; found: C 64.24
d
128.13, 128.93, 132.33, 152.48, 174.16, 178.72, MS m/z
(%): 425.0 (M + Na+), C20H15ClO3S2 (M, 402.9); anal. calcd.
for C20H15ClO3S2 C 59.62, H 3.75; found: C, 59.32 H 3.87.
4.1.5. 2-Chloro-5-ethoxy-3,6-dimorpholinocyclohexa-2,5-
diene-1,4-dione (9), 2-chloro-3,5,6-trimorpholinocyclohexa-
2,5-diene-1,4-dione (10), and 2,3,5,6-
References
tetramorpholinocyclohexa-2,5-diene-1,4-dione (11)
Compounds 9, 10, and 11 were synthesized by the
reaction of 0.100 g (0.38 mmol) 2,6-dichloro-3,5-
diethoxy-1,4-benzoquinone (4) with 0.066 g (0.76 mmol)
morpholine.
[1] M. Batra, P. Kriplani, C. Batra, K.G. Ojha, Bioorg. Med. Chem. 14 (2006)
8519.
[2] Y.P. Wan, T.H. Porter, K. Folkers, Proc. Natl. Acad. Sci. USA 71 (1974) 952.
[3] C.K. Ryu, A. Kim, A.H. Im, J.Y. Kim, Bioorg. Med. Chem. Lett. 22 (2012)
5777.
[4] Z.L. You, D.M. Xian, M. Zhang, X.S. Cheng, X.F. Li, Bioorg. Med. Chem. 20
(2012) 4889.
[5] C. Ibis, A.F. Tuyun, Z.O. Gunes, H. Bahar, M.V. Stasevych, R.Y. Musya-
novych, O.K. Porokhnyavets, V. Novikov, Eur. J. Med. Chem. 46 (2011)
5861.
9: yield 0.043 g (32%); brown oil; IR (Film)
(CHaliphatic), 1649 (C5O), 1496 (C5C) cmÀ1 1H NMR
(499.74 MHz, CDCl3) 1.27–1.30 (t, J = 7.32, 3H,
n 2978
;
d
1CH3CH2O–), 3.40–3.42 (t, J = 4.88, 4H, 2CH2N–), 3.49–
3.51 (t, J = 4.88, 4H, 2CH2N–), 3.71–3.76 (t, J = 4.88, 8H,
4CH2O–), 3.84–3.88 (q, J = 7.32, 2H, 1CH3CH2O–); 13C
[6] W. Ma, H. Zhou, Y.L. Ying, D.W. Li, G.R. Chen, Y.T. Long, H.Y. Chen,
Tetrahedron 67 (2011) 5990.
[7] R.A.J. Smith, G.F. Kelso, A.M. James, M.P. Murphy, Methods Enzymol.
382 (2004) 45.
[8] G. Burnstock, Curr. Top. Med. Chem. 4 (2004) 793.
[9] V.K. Tandon, H.K. Maurya, D.B. Yadav, A. Tripathi, M. Kumar, P.K. Shukla,
Bioorg. Med. Chem. Lett. 16 (2006) 5883.
NMR (125 MHz, CDCl3)
d 15.51, 51.68, 52.01, 67.71,
67.80, 116.20, 140.07, 141.17, 147.31, 178.41, 216.2; MS
m/z (%): 356.82 (M+), C16H21ClN2O5 (M, 356.80); anal.
calcd. for C16H21ClN2O5 C 53.86, H 5.93; found: C 53.78,
H 5.90.
[10] J.A. Valderrama, H. Leiva, J.A. Rodriguez, C. Theoduloz, G.S. Hirshmann,
Bioorg. Med. Chem. 16 (2008) 3687.
10: yield 0.045 g (30%); dark green oil; IR (Film)
(CHaliphatic), 1651 (C5O), 1489 (C5C) cmÀ1 1H NMR
(499.74 MHz, CDCl3) 3.05–3.07 (t, J = 4.88, 4H, 2CH2N–),
n 2974
[11] V.K. Tandon, S. Kumar, N.N. Mishra, P.K. Shukla, Eur. J. Med. Chem. 56
(2012) 375.
[12] K. Ganesh, C. Balraj, A. Satheshkumar, K.P. Elango, J. Mol. Struct. 1035
(2012) 157.
;
d
3.38–3.40 (t, J = 4.88, 4H, 2CH2N–), 3.46–3.48 (t, J = 4.88,
4H, 2CH2N–), 3.66–3.68 (t, J = 4.88, 4H, 2CH2O–) 3.71–3.75
[13] A.P. Neves, M.X.G. Pereira, E.J. Peterson, R. Kipping, M.D. Vargas, F.P.
Silva, J.W.M. Carneiro, N.P. Farrell, J. Inorg. Biochem. 119 (2013) 54.
[14] M. Tetef, K. Margolin, C. Ahn, S. Akman, W. Chow, L. Leong, R.J. Morgan,
J. Raschko, G. Somlo, J.H. Doroshow, Invest. New Drugs 13 (1995) 157.
[15] K.R. Hande, Biochim. Biophys. Acta 1400 (1998) 173.
[16] R.N. Hanson, E. Hua, J.A. Hendricks, D. Labaree, R.B. Hochberg, Bioorg.
Med. Chem. 20 (2012) 3768.
(m, 8H, 4CH2O–); 13C NMR (125 MHz, CDCl3)
d 50.78,
52.07, 67.76, 67.77, 116.94, 134.59, 144.61, 148.05, 178.73,
180.77; MS m/z (%): 420.24 (M + Na+), C18H24ClN3O5 (M,
397.85); anal. calcd. for C18H24ClN3O5 C 54.34, H 6.08;
found: C 54.12, H 6.15.
[17] C.K. Ryu, S.K. Lee, J.Y. Han, J.Y. Lee, S.H. Jeong, Bioorg. Med. Chem. Lett.
15 (2005) 2617.
11: yield 0.034 g (20%); brown oil [33]; IR (Film)
n
2925
[18] K. Matsumoto, T. Choshi, M. Hourai, Y. Zamami, K. Sasaki, T. Abe, M.
Ishikura, N. Hatae, T. Iwamura, S. Tohyama, J. Nobuhiro, S. Hibino,
Bioorg. Med. Chem. Lett. 22 (2012) 4762.
[19] X. Li, S.L. Zheng, X. Li, J.L. Li, O. Qiang, R. Liu, L. He, Eur. J. Med. Chem. 54
(2012) 42.
(CHaliphatic), 1672 (C5O), 1479 (C5C) cmÀ1; MS m/z (%):
449.70 (M+), C22H32N4O6 (M, 448.51); anal. calcd. for
22H32N4O6 C 58.91, H 7.19; found: C, 58.84 H 7.08.
C
Please cite this article in press as: Bayrak N, et al. Spectroscopic and structural aspects of the reactions of 1,4-quinones
with sulfur and nitrogen nucleophiles. C. R. Chimie (2014), http://dx.doi.org/10.1016/j.crci.2013.10.022

G Model
CRAS2C-3855; No. of Pages 7
N. Bayrak et al. / C. R. Chimie xxx (2014) xxx–xxx
7
[20] Z.L. You, D.M. Xian, M. Zhang, X.S. Cheng, X.F. Li, Bioorg Med Chem. 20
(2012) 4889.
[21] Y.S. El-Sayed, Spectrochim. Acta 78 (2011) 1227.
[22] E.M. Nour, M.S. Refat, J. Mol. Struct. 994 (2011) 289.
[23] K. Ganesh, C. Balraj, K.P. Elango, Spectrochim. Acta A 79 (2011)
1621.
[24] K. Ganesh, C. Balraj, A. Satheshkumar, K.P. Elango, J. Mol. Struct. 1033
(2013) 312.
[25] K. Khigasi, K. Baba, A. Renbaum, Kvantovaya Organicheskaya Khimiya
(Quantum Organic Chemistry), Izd. Mir, Moscow, 1967p. 369.
[26] N.M. Ruvalcaba, G. Cuevas, I. Gonzalez, M.A. Martinez, J. Org. Chem. 67
(2002) 3673.
[27] Y. Izumi, H. Sawada, N. Sakka, N. Yamamotto, T. Kume, H. Katsuki, S.
Shimohama, A. Akaike, J. Neurosci. Res. 79 (2005) 849.
[28] P. Kebarle, S. Chowdhury, Chem. Rev. 87 (1987) 513.
[29] F.S. Goksel, C. Ibis, N.A. Bayrak, Phosphorus Sulfur Silicon 180 (2005)
1961.
[30] F.S. Goksel, N. Bayrak, C. Ibis, Phosphorus Sulfur Silicon 189 (1) (2014)
113.
[31] C. Ibis, M. Yıldız, C. Sayıl, Bull. Korean Chem. Soc. 30 (2009) 2381.
[32] A.Y. Berlin, A.N. Makarova, Zh. Obshch. Khim. 30 (1960) 1380.
[33] K. Wallenfels, W. Draber, Tetrahedron 20 (1964) 1889.
Please cite this article in press as: Bayrak N, et al. Spectroscopic and structural aspects of the reactions of 1,4-quinones
with sulfur and nitrogen nucleophiles. C. R. Chimie (2014), http://dx.doi.org/10.1016/j.crci.2013.10.022