Electrosynthesis of a Biaurone by Controlled Dimerization of Flavone: Mechanistic Insight and Large-Scale Application

Article abstract of DOI:10.1021/acs.joc.0c01220

The electrochemistry of flavone (1) has been carefully investigated at glassy carbon cathodes in dimethylformamide containing 0.10 M tetra-n-butylammonium tetrafluoroborate as supporting electrolyte. In this medium, a cyclic voltammogram for a reduction of 1 exhibits a reversible cathodic process (Epc = -1.58 V and Epa = -1.47 V vs SHE) that is followed by an irreversible cathodic peak (Epc = -2.17 V vs SHE). When water (5.0 M) is introduced into the medium, the first peak for 1 becomes irreversible (Epc = -1.56 V vs SHE), and the second (irreversible) peak shifts to -2.07 V vs SHE. Bulk electrolyses of 1 at -1.60 V vs SHE afford flavanone, 2′-hydroxychalcone, 2′-hydroxy-3-phenylpropionate, and two new compounds, namely (Z)-1,6-bis(2-hydroxyphenyl)-3,4-diphenylhex-3-ene-1,6-dione (D1) and (Z)-2,2′-(1,2-diphenylethene-1,2-bis(benzofuran-3(2H))-one) (D2), obtained in significant amounts, that were characterized by means of 1H and 13C NMR spectrometry as well as single-crystal X-ray diffraction. Along with the above findings, we have proposed a mechanism for the electroreduction of 1, which has been further corroborated by our quantum mechanical study.

Full text of DOI:10.1021/acs.joc.0c01220

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Article
Electrosynthesis of a Biaurone by Controlled Dimerization
of Flavone: Mechanistic Insight and Large-Scale Application
Seyyedamirhossein Hosseini, Bishnu Thapa, Maria Jose Medeiros, Erick
M. Pasciak, Michael A. Pence, Eric B. Twum, Jonathan A. Karty, Xinfeng
Gao, Mohammad S. Mubarak, Krishnan Raghavachari, and Dennis G Peters
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01220 • Publication Date (Web): 20 Jul 2020
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Electrosynthesis of a Biaurone by Controlled Dimerization of Flavone:
Mechanistic Insight and Large-Scale Application
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Seyyedamirhossein Hosseini,† Bishnu Thapa,† Maria J. Medeiros,‡ Erick M. Pasciak,† Michael A.
Pence,† Eric B. Twum,† Jonathan A. Karty,† Xinfeng Gao,† Krishnan Raghavachari,† Dennis G.
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Peters●,† and Mohammad S. Mubarak, *†§
,
†Department of Chemistry, Indiana University, Bloomington, Indiana, 47405, United States
‡Departamento de Química, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal
§Department of Chemistry, The University of Jordan, Amman 11942, Jordan
*Corresponding Author Email: mmubarak@indiana.edu; mmubarak@ju.edu.jo
●Prof. Dennis G. Peters passed away on 04/13/2020
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ABSTRACT
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Electrochemistry of flavone (1) has been carefully investigated at glassy carbon cathodes in
dimethylformamide (DMF) containing 0.10 M tetra-n-butylammonium tetrafluoroborate
(TBABF4) as supporting electrolyte. In this medium, a cyclic voltammogram for a reduction of 1
exhibits a reversible cathodic process (Epc = –1.58 V and Epa = –1.34 V vs. SHE) that is followed
by an irreversible cathodic peak (Epc = –2.17 V vs. SHE). When water (5.0 M) is introduced into
the medium, the first peak for 1 becomes irreversible (Epc = –1.56 V vs. SHE), and the second
(irreversible) peak shifts to –2.02 V vs. SHE. Bulk electrolyses of 1 at –1.60 V vs. SHE afford
flavanone, 2´-hydroxychalcone, 2´-hydroxy-3-phenylpropionate, and two new compounds,
namely (Z)-1,6-bis(2-hydroxyphenyl)-3,4-diphenylhex-3-ene-1,6-dione (D1) and (Z)-2,2´-(1,2-
diphenylethene-1,2-bis(benzofuran-3(2H))-one) (D2), obtained in significant amounts, that were
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1
characterized by means of H and 13C NMR spectrometry as well as single-crystal X-ray
diffraction. Along with the above findings, we have proposed a mechanism for the electroreduction
of 1, which has been further corroborated by our quantum mechanical study.
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INTRODUCTION
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Flavonoids are biologically important molecules found in various natural sources, such as
the extracts of citrus fruits.1,2 Some flavonoids (Scheme 1) exhibit significant anticancer and anti-
inflammatory properties.3–8
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Scheme 1. Pharmaceutically important derivatives of flavone.
Among these flavonoids, aurone and biaurone are attractive subclasses due to their natural
abundance and potent biological activity.9–13 Furthermore, these compounds are interesting
reagents for the synthesis of more complex structures such as spirocycles and
benzofuroazepinones.14–17 Shown in Scheme 2 is the possible approach to form a biarouene.18–21
To form an aurone, an oxidative intermolecular cyclization of 2′-hydroxychalcones or various
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condensation approaches have proven to be effective. Then an electroreductive dimerization or a
radical-radical coupling reaction can be used to yield the indicated biaurone. However, these
synthetic methods are associated with numerous obstacles such as low yield, use of expensive
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catalysts, and low atom economy.
Furthermore, the use of flavone to form a biaroune, a
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process that involves opening a six-membered ring and its closure to form a five-member ring
conjugated with a double bond and subsequent dimerization, has not yet been reported .
Scheme 2. Possible synthesis of biaroune from various starting materials including a: present work (TBABF4-
DMF/Water (10%), E = –1.10 V), b: Yatabe et al.18 (O2, Au-Pd catalyst immobilized onto CeO2), c: Cheng et
al.19 (piperidine, HOAC, benzene), d: Harkat et. al.20 (AuCl, K2CO3, MeCN), e: Weng et al.21 (CuI, 1,10-
phenanthroline, Cs2CO3, 105 °C, N2), f: Qi et al.22 (Pd(PPh3)4, Et3N, Ac2O, Toluene, 80 °C),
On the other hand, electrosynthesis of relatively complex molecules such as heterocycles
has gained momentum in recent years.26–29 In comparison with conventional methods of synthesis,
electrosynthesis features a selective, fast, and green alternative since catalysts and reagents
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required for the reaction can be minimized by the use of proper electrochemical methodology and
suitable electrode materials.30,31 In this context, it is worth mentioning that electrosynthesis can
be accomplished via the two alternative modes of constant-current or controlled-potential
electrolysis.32 Constant-current electrolysis is technically less challenging and offers a faster
approach to the formation of certain molecules. However, this feature can come at the cost of low
selectivity. Accordingly, controlled-potential electrolysis (CPE) is the method of choice for the
synthesis of complex molecules where higher selectivity is desirable.
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Based on the above discussion, we report herein the first successful one-pot
electrosynthesis of a biaurone via application of CPE. We have thoroughly examined the
electrochemistry of an ether moiety couple with an α,β-unsaturated ketone group in N,N-
dimethylformamide (DMF) containing 0.10 M TBABF4 with the aid of cyclic voltammetry and
controlled-potential (bulk) electrolysis. Furthermore, we have investigated the effect of several
proton donors on the reaction yield and product distribution. For each electrolysis, components of
the mixture were separated employing normal-phase liquid chromatography, and each separated
species was characterized with the aid of gas chromatography–mass spectrometry (GC–MS), high-
performance liquid chromatography–electrospray ionization–mass spectrometry (HPLC ESI
MS), and NMR spectrometry. Finally, we have used NMR spectroscopy and single-crystal X-ray
diffraction data to establish the molecular structure of the target biaurone.
RESULTS AND DISCUSSION
Cyclic Voltammetric Studies. Displayed in Fig. 1 are cyclic voltammograms
obtained at 100 mV s–1 for reduction of 5.0 mM flavone (1, Scheme 4) or flavanone (2, Scheme
4) in DMF containing 0.10 M TBABF4 at a glassy carbon cathode. Flavone exhibits a quasi-
reversible redox couple (Epc = −1.58 V and Epa = −1.34 V vs. SHE) (S24–S26 and Table S2) that
is followed by an irreversible cathodic peak (Epc = −2.17 V vs. SHE). Upon addition of an excess
of water to the solution of 1 (dotted red trace), the potential of both cathodic peaks shifts to a less
negative value. Additionally, the corresponding anodic peak (at −1.34 V) disappeared. Moreover,
integration of the area under each cathodic peak revealed that the first redox couple involves a one-
electron transfer, whereas the second peak corresponds to a two-electron reduction process.
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Figure 1. Cyclic voltammograms recorded at 500 mV s–1 for reduction of 5.0 mM flavone at a glassy carbon
electrode (area = 0.071 cm2) in DMF containing 0.10 M TBABF4. Black voltammogram (unbroken line) shows
behavior in the absence of added water, red dotted voltammogram shows behavior in the presence of 5.5 M
added water, and blue dashed trace shows electrochemical behavior of the flavanone (2) in absence of water.
Each scan goes from –0.50 to –2.50 to –0.50 V vs. SHE.
Controlled-Potential (Bulk) Electrolyses of Flavone (1). Bulk electrolyses of flavone at
potentials corresponding to the first cathodic peak in the presence of an added proton donor led to
the formation of several products. As shown in Table 1, the amounts of unreacted flavone as well
as products D1 and D2 (structures are shown in Scheme 4) increase as pKa of the proton donor
increases. However, the use of a less potent proton donor leads to the formation of lower yields
of flavanone and compounds 3 and 4 (structures displayed in Scheme 4).
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Table 1. Coulometric Data and Product Distributions for Controlled-Potential
(Bulk) Electrolyses of 5.0 mM Flavone (1) at Reticulated Vitreous Carbon
Cathodes Held at –1.60 V vs. SHE in DMF Containing 0.10 M TBABF4
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Product distribution (mol.%)a
Enetry Proton donor
pKa
nb
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41
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4
D1e
D2e
1
2
CH3COOH
HFIPc
H2O
13.36 2.50 trace 50
25
18
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Trace
Trace
18.8 2.10
32.2 3.06
32.2 4.12
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3
15 (3.2 mg)
23 (4.9 mg)
16 (3.4 mg)
8 (1.8 mg)
42 (9.7 mg)
35 (8.1 mg)
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25
4d
H2O
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a1 = flavone, 2 = flavanone, 3 = 2´-hydroxychalcone, 4 = 2´-hydroxy-3-phenylpropionate, D1 = 1,6-
bis(2-hydroxyphenyl)-3,4-diphenylhexane-1,6-dione, D2 = (Z)-2,2´-(1,2-diphenylethane-1,2-diyl)bis-
b
c
(benzofuran-3-(2H)-one). Average number of electrons per molecule of substrate. HFIP = 1,1,1,3,3,3-
d
hexafluoro-2-propanol. Controlled-potential electrolysis carried in presence of adventitious oxygen.
e Numbers in parentheses show yields in milligrams for electrosynthesis of D1 and D2.
Products D1 and D2 were crystallized through a slow solvent-evaporation method (see
Supporting Information). Both samples (D1 and D2) were characterized by single-crystal X-ray
diffraction (Fig. S1–S4), high-resolution mass spectrometry, as well as NMR spectroscopy (Fig
S5–S14). Compound D1 is a linear hydrodimer of 4 with a P21/n space group, whereas D2 has the
structure of a biaurone, which is a cyclized hydrodimer whose crystal structure belongs to the pbca
space group. However, differences in the molecular structures of D1 and D2 rule out the possibility
of intermolecular conversion of these two species. Further electrochemical studies were performed
on D1 and D2 to confirm the validity of this hypothesis. We further probed the role of proton
donors on the yield of the biaurone (D2) by varying the water concentration in the supporting
electrolyte (Table 2). Data in Table 2 revealed that the yield of D2 increases with increasing
proton-donor concentration. However, with water concentrations above 5.50 M, no significant
change either in yield or product ratio was observed. Based on these results, we conclude that the
optimal condition to produce compound D2 is to use a flavone-to-proton donor ratio of 1:1000.
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––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
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Table 2. Coulometric Data and Product Distributions for Controlled-
Potential (Bulk) Electrolyses of 5.0 mM Flavone (1) at Reticulated
Vitreous Carbon Cathodes Held at –1.60 V vs. SHE in DMF Containing
0.10 M TBABF4 and an Excess of Water
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entry
[H2O], M
0.10
na
D2 to D1 ratio
1.8:1
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3.31
3.52
3.71
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1:1.2
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1:1.8
aAverage number of electrons transferred per molecule of flavone (1).
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
Proton-Donor Effect. As shown by previous results, the electrochemical behavior of
the flavone is greatly influenced by the nature and concentration of the proton donor. When water
was employed at the optimal concentration (5.5 M), two surprising products, including D1 and
D2, were formed. Electrochemistry of enones has been the subject of several publications.33–37
Enones exhibit two cathodic peaks roughly around –0.90 V and –1.70 V vs. SHE in the absence
of proton donors (a sample electrochemical behavior of these molecules that bear the enon moiety
is shown in Fig. S27). It was shown that the first cathodic event is due to the reduction of the
activated double bond that affords a radical anion (one electron process). The second peak arises
from the reduction of the carbonyl group to form the corresponding alcohol (a two-electron
process). However, for flavone (1), an ether group is coupled with the enone moiety; hence, the
electrochemical nature of the first reduction peak may differ from that of α,β-unsaturated carbonyls
(R1CH=CHCOR2). We carried a number of electrochemical studies to elucidate the underlying
electrochemical mechanism of electron transfer in flavone.
Electrochemical behavior of flavone shows a close dependency on the concertation of
water (Fig. 2). In parallel with increasing water content of the supporting electrolyte, the
reversibility of the redox peak at –1.50 V declines. Additionally, higher scan rates are needed to
probe the oxidation peak at –1.53 peak (Fig. S28–S29). These observations confirm that the first
peak at –1.50 V involves a slow reduction process and the rate of electrochemical process and
stability of reduced species depends on the concentration of the proton donor. Also, significant
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displacement of the cathodic peak position with changes in water concentration confirms that the
reduction process involves a proton-coupled electron transfer reaction (i.e., 166 mV comparing
peak positions in 100 mM and 4.0 M). With respect to relative thermodynamic stability of the
intermediates (S32), we believe the first reduction peak at –1.50 V involves formation 1a and 2b
as shown in Scheme 3.
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Scheme 3. Reduction of flavone at the first cathodic peak (–1.50 V vs. SHE) in DMF-TBABF4 (0.10 M) and in
presence of water at 4.0 M and higher concentrations.
From a thermodynamic point of view, 2b is more stable than 1a; however, standard
reduction potential of these intermediates is well below –1.50 V (–0.44 V and –0.78 V
respectively). Consequently, it is reasonable to assume that both of these intermediates can form,
and possibly interconvert, under our working conditions.
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Figure 2. Cyclic voltammograms recorded for 5.0 mM flavone at in presence of various amount of water
including 100 mM (solid black voltammogram), 1.0 M (dotted red line), 2.50 M (dashed blue line), and 4.0 M
(dashed-dotted green trace) at a glassy carbon electrode (area = 0.071 cm2) in DMF containing 0.10 M TBABF4.
Secondary reduction peak, indicated with an asterisk, appears at water concentrations higher than 4.0 M. Height
of the reversible oxidation peak declines in accordance with increasing water concentration as indicated by the
diagonal arrow. Also, the first reduction peak shifts 160 mV with increasing water concentration, indicating
dependency of the first peak on water concentration.
Furthermore, in the presence of the optimal water concentrations (above 4.0 M) and slow
scan rates (than 100 mV/s and slower), a new reduction peak at −1.75 V arises (Fig. 2, peaks
shown by an asterisk). The nature of this peak was examined with the aid of the slow scan rate
studies (Fig. 3). As the potential sweep rate decreases, the magnitude and the area under the new
peak increase. Eventually, at scan rates slower than 10 mV/s, the area and the current for potential
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peaks located at –1.50 V and –1.75 V become comparable. As the result, we concluded that upon
formation, 1a or 2b undergoes a slow chemical reaction to yield a new species that is reducible at
potentials close to our working conditions.
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Figure 3. Cyclic voltammograms recorded for 5.0 mM flavone at 5 mV/s (solid black voltammogram), 10
mV/s (dotted blue line), 20mV/s (dashed red trace), and 100 mV/s (dashed-dotted green trace) at a glassy carbon
electrode (area = 0.071 cm2) in DMF containing 0.10 M TBABF4 and 5.5 M water. Reversible oxidation peak
appears at 1.0 V/s as a small peak starting from a scan rate of 500 mV/s.
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The electrochemical behavior of the flavone in the presence of a more potent proton donors
including acetic acid and HFIP also shows the same lack of reversibility (Fig. S30). Nevertheless,
a much lower concentration is needed to carry out the same reduction process. Considerable
cathodic potential shift and dependency of the electrochemical behavior to the pKa of proton donor
confirms that the reduction process has PCET nature. Furthermore, electrolysis of flavone affords
3 and 4 once more potent proton donor (i.e. acetic acid or HFIP) was employed. This observation
confirms that the first reduction peak is a two-step process and includes (a) reduction of the
conjugated double bond and (b) cleavage of ether moiety. With regards to the result of DFT
analysis (see below), in the presence of the potent proton donor, the formation of 1a or 2b is
followed rapidly by dissociation of the C–O bond, which then affords 3 and 4. These assumptions
were further confirmed by considering the electrochemical behavior of the flavanone (2). The only
difference between the structure of 1 and 2 is the lack of the conjugated double bond between
carbonyl and ether moieties. Cyclic voltammograms of flavanone show two irreversible reduction
peaks at –1.50 and –2.51 V (Fig. 1, blue dashed trace). Lack of reversible redox peak at –1.50 V
confirms that reduction of flavanone involves cleavage of the ether moiety. Electrolysis of 2 at the
optimal water concentration (above 4.0 M) and –1.50 V affords D1 which confirms the hypothesis
about the sequential reduction mechanism that ultimately leads to the cleavage of the C–O bond.
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Mechanistic Aspects of the Electroreduction of Flavone (1). Using a combination of
experimental evidence and computational analysis with the B3LYP density functional theory (see
Supporting Information), we have proposed a mechanism for the electroreduction of flavone
(Scheme 4). This mechanism accounts for the formation of the various electrolysis products
obtained under different experimental conditions. It is important to note that most of the reaction
steps involving an electron and proton transfer are discussed as a proton-coupled electron transfer
(PCET) event to assess if the process is favorable with our applied electrochemical potential.
However, since many of the reduction intermediates are highly unstable, one must consider the
occurrence of hydrogen-atom transfer (HAT) reaction or a competition between HAT and PCET
events. According to Scheme 4 (i.e. S35), in the first step of electroreduction, 1 accepts an electron,
which is followed by a proton transfer to form the key intermediate, 1a. In the presence of a weak
proton donor such as water (indicated by dashed violet line), 1a undergoes keto–enol
transformation to afford intermediate 2b (ca. ∆G = +2.07 kcal/mol, P1) which further dimerizes
to form I1 (ca. ∆G = –8.17 kcal/mol). Next, in two consecutive steps, I1 accepts two electrons and
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two protons in total (i.e., two successive PCET processes) to yield I2. Both of these steps are
표
calculated to be significantly favorable (
= –0.05 V, and +1.61 V vs. SCE, respectively)
퐸푃퐶퐸푇
under our reaction conditions. We determined the structure of I2 with the aid of several
spectroscopic techniques, including one- and two-dimensional NMR and high-resolution mass
spectrometry (see Supporting Information Figs. S15–S20). In the following step, I2 undergoes two
favorable PCET reactions accepting two-electrons and two protons in a stepwise fashion to form
D1.
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Scheme 4. The stepwise mechanism for electroreduction of flavone in the presence of a proton donor. Blue
dashed lines show the reaction pathway in the presence of less potent proton donors, whereas the red dashed line
represents electrolysis pathway in an acidic medium. 2 = flavanone, 3 = 2´-hydroxychalcone, 4 = 2´-hydroxy-
3-phenylpropionate, D1 = 1,6-bis(2-hydroxyphenyl)-3,4-diphenylhexane-1,6-dione, D2 = (Z)-2,2´-(1,2-
diphenylethane-1,2-diyl)bis-(benzofuran-3-(2H)-one).
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Flavone can afford D2 by the reaction mechanism shown in P2 (Scheme 4, S36).
In parallel to the reaction described above, 1a affords intermediate 2cc in a two-step reaction
process involving the formation of an oxo-radical intermediate 2c-o (ca. ∆GTS1 = +16.79 kcal/mol;
∆G1a2c-o = 2.04 kcal/mol) which is followed by a ring-closure reaction (ca. ∆GTS2 = +15.43
kcal/mol; ∆G1a2c-o = 3.38 kcal/mol). These two steps are computed to be significantly more
favorable over the concerted pathway involving a six- to five-member ring transformation (∆GTS3
= +53.47 kcal/mol). Upon formation, 2cc can dimerize directly to afford a new specie; however,
we assume the intermediate 2cc undergoes a keto-enol tautomerization to afford more
thermodynamically stable intermediate 2cc• which then dimerizes to give 2ccc (Fig. S36).
Transformation of 2ccc to D2 is a sequential oxidation reaction which may involve three
intimidates including 2ccc′, 2ccc′′, 2ccc′′′ (Fig. S37). We believe oxidation of the intermediate
2ccc under our working conditions can happen via two concurrent pathways including (i) hydrogen
atom abstraction by electrogenrated radicals and (ii) reactions with adventitious oxygen radicals
in the catholyte.
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As shown in Scheme 3 and 4, reduction of flavone affords number of radical-bearing
intermediates. Our analysis indicates that almost all of the electrogenerated radical intermediates
can exothermically accept the hydrogen atom from 2ccc and its following intermediates to give
D2 (Fig. S38, ∆GHAT ranges from –34.99 to –10.28 kcal/mol). An example for hydrogen-atom
abstraction via electrogenerated radicals is shown in Scheme 5.
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Scheme5. Hydrogen atom abstraction via electrogenerated radicals. Shown in the left panel is an example for
reaction free energy of I2 radical intermediate and 2ccc. As indicated in the right panel, oxidation of 2ccc
involves a sequential 4-step reaction (shown by the dotted green arrow) to afford D2. Structures of 2ccc, 2ccc′,
2ccc′′, and 2ccc′′′ are shown in S37. A complete list for HAT reaction free energies is shown in Fig. S38.
As mentioned earlier, another possibility for the oxidation of 2ccc to D2 involves
participation of the adventitious oxygen. Cyclic voltammetry of oxygen in our working condition
shows two reduction peak at –0.70 V and –1.50 V (Fig. S39). The second peak for reduction of
oxygen matches well with the potential we employed to electrolyze flavone. An electrolysis was
carried in the presence of the catalytic amount of the oxygen at –1.5 V to investigate the interaction
of the reduced oxygen and flavone (Scheme 2, Supporting Information). Comparing with the
controlled experiment (Table 1, entry 3), the amount of the unreacted flavone has increased from
10 to 25% when the electrolysis was carried out in presence of oxygen (Table 1, entry 4).
Furthermore, D2 still forms in a considerable amounts which confirms the involvement of
adventitious oxygen. Finally, the n-value for this experiment is elevated which can be attributed
to direct oxygen reduction. However, increasing the ratio of oxygen, e.g. replacing the Ar stream
with a stream of oxygen in the gas mixture, disrupts the electrolysis; negligible amount of flavone
electrolyzes to afford 2 and the electrolysis affords substantial amounts of water.
Reduction of flavone affords a number of stable intermediates, hence it is possible to
propose various reaction mechanisms to account for the appearance of D1 and D2. For example,
one can argue that over-reduction of D2 can also afford D1. While we are unable to altogether
reject this assumption, we believe this transformation is not likely to happen under our
experimental conditions. This argument is also corroborated by our experimental observations. As
mentioned earlier, we detected insignificant amounts of I2. However, electrolysis of I2 under our
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working conditions solely afforded D1, and no trace of D2 was found. Furthermore, purified D2
did not undergo a further reduction under our working conditions. These observations nullify, to a
reasonable degree of confidence, the possibility of cross transformation of D1 and D2.
Furthermore, formation of the product D2 results from an oxidation, possibly involving a
combination of hydrogen atom abstraction by intermediates in solution during the reaction and
oxidation by oxygen radicals, either during the electrolysis or following the reaction. However,
more work would need to be done to test the stability of 2ccc in order to gain a better understanding
of this portion of the mechanism.
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A shown in Table 1, flavanone forms in a wide range of proton donors. To account for this
observation, we propose the step-by-step mechanism shown in P3. In the presence of a proton, 1a
undergoes reduction (ca. Eo= 1.47 V vs. SCE) along with uptake of a proton or overall a PCET
표
process to give flavanone (2, pK = 44.91; 푃퐶퐸푇 = +1.18 V). Once flavone was electrolyzed in
퐸
a
the presence of HFIP or acetic acid, large amount of flavanone, 3 and 4 form. To account for this
observation, we propose detailed mechanism shown in P4 (Scheme 4). In the presence of a potent
proton donor, 1a undergoes immediate protonation; this step then can lead to saturation of the
conjugated double bond (formation of flavanone) or rapid ring opening to yield 3. Once formed,
표
3 acquires two electrons and two protons in two successive and favorable PCET steps ( 푃퐶퐸푇 = –
퐸
0.48 V, and +1.33 V vs. SCE, respectively) to give 4 (S34). At a potential of –1.20 V vs. SCE (i.e.,
–1.60 V vs. SHE), compound 4 is inactive and cannot undergo further reduction.
In conclusion, a number of pieces of evidence helped us to propose Scheme 4 to account
for the product distribution reported in Table 2. These include but are not limited to (a) product
distribution as a function of the strength and concertation of proton donor, (b) effect of proton
donor concentration and strength on the reversibility of the first redox peak, (c) appearance of new
redox peak and scan rate studies, and (d) thermodynamic stability of intermediates. As shown,
nature and concentration of the proton donor can be utilized as a facile tool to control reactivity of
the intermediate. In this context, dimers of D1 and D2 will form once flavone was electrolyzed in
DMF-TBABF4 that includes large excess of water as the proton donor (4.0 M or above).
Gram-scale Synthesis. To scale-up the electrosynthesis, we used higher concentrations of
the starting materials, while the concentration of proton donor and supporting electrolyte remained
the same as before. Fig. 4 compares cyclic voltammograms for the reduction of 10, 30, and 100
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mM of flavone. At 10 mM, cyclic voltammogram mimics those seen in Fig. 1. However, at higher
concentrations, the first two peaks merge to form a single irreversible reduction peak while the
position of the third peak remains unchanged. Electrolyses at high concentrations were carried out
at –1.60 V, and our analysis proved that with increasing flavone concentration, the yield of reaction
decreases (Table 3).
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Figure 4. Cyclic voltammograms recorded at 100 mV s–1 for reduction of flavone at a glassy carbon electrode
(area = 0.071 cm2) in DMF containing 0.10 M TBABF4 in presence of 5.5 M water. Black voltammogram
(unbroken line) was obtained at 10 mM, blue trace (dashed line) shows the behavior of 30 mM of flavone, and
dotted red trace represents electrochemical behavior of 1 at 0.1 M. Each scan goes from –0.50 to –2.50 to –0.50
V vs. SHE.
This could be due to partial meltdown of the methylcellulose plug that separates the
cathode and anode component, as electrolysis in higher concentration involves the passage of high
current density. A meltdown of the permeable membrane will allow movement of reduced
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intermediates from the cathode compartment to anode where they will revert to their original form
as the result of oxidation.
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Table 3. Product Distributions for Controlled-Potential (Bulk) Electrolyses of carious
concentrations of Flavone (1) at Reticulated Vitreous Carbon Cathodes Held at –1.6 V
vs. SHE in DMF Containing 0.10 M TBABF4 and water concentration of 5.5 M .
Product distribution (wt. %)b
[Flavone]a
10 mM (44.53 mg)
30 mM (133.60 mg) 23
100 mM (445 mg) 34
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4
D1c
D2c
42 (18.70 mg)
31 (41.41 mg)
22 (97.91 mg)
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23 (10.24 mg)
19 (25.38 mg)
15 (66.75mg)
a: All experiments were carried out in a 20 ml electrolysis cell.
b: Products of the electrolysis were separated with the aid of the normal phase chromatography, dried
under vacuum and the purity of the each product was verified with the aid of H1 NMR. The weight of
purified resultant was divided by flavone to get corresponding weight percent.
c: The amount of the electrosynthesized D1 and D2 in milligram are reported in parentheses.
CONCLUSIONS
Electroreduction of flavone (1) at carbon cathodes in DMF containing 0.10 M TBABF4 in
the presence of various proton donors yields two new compounds in significant amounts: (Z)-1,6-
bis(2-hydroxyphenyl)-3,4-diphenylhex-3-ene-1,6-dione (D1) and the naturally occurring biaurone
(Z)-2,2´-(1,2-diphenylethene-1,2-bis(benzofuran-3(2H))-one) (D2). In the presence of a potent
proton donor (1,1,1,3,3,3-hexafluoro-2-propanol), ring-opening from the ether terminal followed
by protonation of a conjugated double bond is dominant. On the other hand, in the presence of a
weak proton donor (water), dimerization dominates. More importantly, the optimization of the
flavone-to-proton-donor ratio leads to the formation of more of the natural product biaurone (D2).
Additionally, electrodimerization of flavone can be carried out under mild experimental conditions
at room temperature, and the extent of dimerization can be controlled by a change in the proton
donor. Results from this investigation also revealed that, in the absence of an activated double
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bond (as in flavanone), reduction takes place through the ether moiety. Flavanone (2) undergoes
dimerization when a weak proton donor (H2O) is employed; however, in the presence of a potent
proton donor (HFIP), reduction proceeds via ring-opening and subsequent hydrogenation.
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EXPERIMENTAL SECTION
Reagents. Each of the following reagents (with commercial source and purity in
parentheses) was used as received: dimethylformamide (DMF, EMD Millipore, 99.9%), methyl
cellulose
(Sigma
Aldrich,
95%),
flavone
(Sigmal
,, Aldrich, 95%), flavanone (Sigma Aldrich, 98%), 2¢-hydroxychalcone (Alfa Aesar, 98%), 2-
hydroxy-3-phenylpropiophenone (TCI, >98%). Tetra-n-butylammonium tetrafluoroborate
(TBABF4, GFS Chemicals, 98.5%), used as supporting electrolyte, was recrystallized from ethyl
acetate–diethyl ether and stored under vacuum at 80 ºC to remove traces of water. Deaeration of
all solutions for cyclic voltammetry and controlled-potential (bulk) electrolyses were carried out
with zero-grade argon (Air Products).
Cells, Electrodes, Instrumentation, and Procedures. Detailed information about cells,
electrodes, instrumentation, and procedures for cyclic voltammetry and controlled-potential
electrolysis are described in previous publications.38–42 In summary, cyclic voltammograms were
obtained with the aid of a Princeton Applied Research Corporation (PARC) model 2273
potentiostat–galvanostat operated by PowerSuite software. All potentials were measured
experimentally with respect to a reference electrode consisting of a cadmium-saturated mercury
amalgam in contact with DMF saturated with both cadmium chloride and sodium chloride; this
electrode has a potential of –0.76 V versus the aqueous saturated calomel electrode (SCE) at
25ºC.43–45 However, all potentials cited in this paper are given with respect to the standard
hydrogen electrode (SHE).
All constant-potential electrolyses were carried out in a divided cell in which anode and
cathode compartments are separated via a permeable membrane made of methyl cellulose and
DMF. Cathode compartment hosts the reference electrode, gas inlet, gas outlet, and a working
electrode. Anode section comprises graphite rode submerged in an oxygen free DMF-TBAB4, and
the bottom of the anode is filled with the permeable membrane. Prior to each electrolysis, catholyte
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was deoxygenated by the introduction of a stream of Ar (Airgas, 99.99% purity grade) while stirred
vigorously. After complete deoxygenation, a desirable potential is applied, which is marked by a
negligible current spike (A in S31). Once the initial current spike decayed to the background level,
flavone (22.22 mg for a 5 mM electrolysis) was dissolved in 2 ml of deaerated catholyte and
injected at once into the cathode compartment. This stage is accompanied by a marked current
spike that is shown by B in S31. During the electrolysis, a stream of Ar remained uninterrupted to
prevent diffusion of oxygen into the electrolysis mixture. Similar protocol was carried out for
electrolyses at higher concentrations of flavone. Controlled-potential (bulk) electrolyses were
performed with the aid of a PARC model 173 potentiostat. A locally written LabView program
was used for the collection of data, which were processed with OriginPro 2018 software.
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Separation, Identification, and Quantitation of Products. At the end of each
controlled-potential electrolysis, the catholyte was hydrolyzed with 1.6 M HCl, extracted into 60
mL of ethyl acetate, and finally washed in succession with three 35-mL portions of brine and 35
mL of water. Then the organic phase was dried over anhydrous sodium sulfate, and the solvent
was evaporated under reduced pressure. Finally, components of the concentrated organic phase
were separated by application of normal phase chromatography. For this mean, concentrated
organic phase load onto a silica (50 µm) and eluted with a programmed mobile phase. Normal
phase chromatography was carried out with application of a Combiflash NextGen300+ (Teledyne
Isco) equipped with a fraction collector. Elution was monitored at two wavelentghe of λ=254 nm
and λ= 280 nm. Typical chromatograms for separation of product mixture and further purification
of D1 and D2 are shown in Supporting Information (S21–S23). Finally, separated fractions were
dried under vaccum at 70 °C and the amount of the electrosynthesized sample has been measured
by weighting the dried material. For all products, the yield of the reaction is shown as mol %
(Table 1), weight % (Table 2). Products of the reaction were identified by means of gas
chromatography–mass spectrometry (GC–MS), various forms of NMR spectroscopy, HRMS
measurements, and single-crystal X-ray diffraction analysis.
NMR spectra were acquired on a 500-MHz Varian Inova spectrometer with
tetramethylsilane (TMS) as an internal standard. Chemical shifts are expressed in δ units, and 1H-
1H coupling constants are given in hertz. GC–MS studies were conducted with a Hewlett–Packard
6890N gas chromatograph, fitted with a 30 m × 0.25 mm i.d. Agilent DB-5 capillary column and
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coupled to a Hewlett-Packard model 5973 inert mass-selective detector operating in electron-
ionization mode (70 eV). HRMS measurements were carried out with the aid of a Hewlett–
Packard 5890 Series II gas chromatograph (Thermo Electron Corporation) equipped with a DB-5
capillary column and coupled to a MAT-95X magnetic-sector mass spectrometer. Single-crystal
data were acquired with a Bruker APEX II Kappa Duo diffractometer equipped with an APEX II
detector at 150 K.
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Characterization of 1,6-bis(2-hydroxyphenyl)-3,4-diphenylhexane-1,6-dione (D1). 1D 1H and
13C{1H}, 2D double-quantum-filtered (dqf) COSY, multiplicity-edited HSQC, and HMBC spectra
1
of D1 are shown in Figs. S5–S9. H and 13C{1H} chemical-shift data are summarized as follows:
1H NMR (500 MHz, chloroform-d): δ 12.15 (s, 1H), 7.66 (dd, J = 8.1, 1.7 Hz, 1H), 7.44 (ddd, J =
8.5, 7.2, 1.7 Hz, 1H), 7.24–7.15 (m, 3H), 6.97 (dd, J = 7.7, 1.8 Hz, 2H), 6.94 (dd, J = 8.5, 1.2 Hz,
1H), 6.86 (ddd, J = 8.1, 7.2, 1.2 Hz, 1H), 3.87 (m, 1H), 3.43–3.38 (m, 2H). 13C{1H} NMR (126
MHz, chloroform-d): δ 204.7 (s), 162.6 (s), 140.6 (s), 136.5 (d), 129.8 (d), 129.1 (d), 128.2 (d),
127.0 (d), 119.5 (s), 119.0 (d), 118.7 (d), 45.3 (d), 41.4 (t). High-resolution ESI–MS exact mass
calculated for C30H25O3 [M – (H2O) + H]+ 433.1804, found 433.1798. White needle crystal,
melting point = 152–153 °C.
The most downfield peak at 204.7 ppm in the 13C{1H} spectrum (Fig. S6) is assigned to the
carbonyl carbon C1´´. In the 1H spectrum (Fig. S5), J-coupling patterns of the four 1H peaks at
7.66, 7.44, 6.94, and 6.86 ppm and the correlations among them in the dqfCOSY spectrum (Fig.
S7) indicate that these protons belong to the 1,2-disubstituted benzene ring. The proton at 7.66
ppm showed a correlation to the carbonyl carbon in the HMBC spectrum (Fig. S9) and is therefore
assigned to H6. Consequently, the other three protons at 7.44, 6.94, and 6.86 ppm can be assigned
to H4, H3, and H5, respectively. From the HSQC spectrum (Fig. S8), these protons are attached
to carbons C3 to C6. In the HMBC spectrum, both H4 and H6 protons are correlated with the
carbon at 162.6 ppm. This carbon is assigned to C2 based on its chemical shift and the correlations
through vicinal CH (3JCH) coupling. In addition, the HMBC spectrum also showed that both H3
and H5 protons are correlated with the carbon at 119.5 ppm; this carbon is assigned to C1.
A single proton signal at 12.15 ppm that shows no correlation to any carbon in the HSQC
spectrum, is assigned to the OH proton. In the HMBC spectrum, three strong correlations to C1,
C2, and C3, respectively, and one weak correlation to C4, were observed.
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In the multiplicity-edited HSQC spectrum (Fig. S8), the negative peak (in blue color) is
undoubtedly assigned to the methylene group; we assign the methylene proton H2´´ correlated to
the proton at 3.87 ppm in the dqfCOSY to H3´´. Carbon C3´´ can be obtained from the HSQC
spectrum. For the HMBC spectrum, the carbonyl carbon showed strong correlation to H2´´
protons and weak correlation to the H3´´ proton, confirming the assignments of this part of the
molecule. It should be noted that the two protons of the methylene group are not exactly
equivalent; second-order effects were seen for the H2´´ and H3´´ peaks in the 1H spectrum.
Two protons at 6.97 ppm showed a correlation in the HMBC spectrum to carbon C3´´.
These protons are assigned to H2´ and H6´. Their directly attached carbons C2´ and C6´ can be
obtained from the HSQC spectrum. In the dqfCOSY spectrum, protons H2´ and H6´ showed a
correlation to the proton signals at 7.20 ppm. Integration of the proton signals at 7.20 ppm
indicated three protons; two were assigned to H3´ and H5´ and the other to H4´. These three
protons are attached to carbons C3´, C5´, and C4´, as can be concluded from the HSQC spectrum.
Carbons C3´ and C5´ are equivalent. Overlapped H3´/H5´ and H4´ peaks were resolved in the
HSQC spectrum. Finally, in the HMBC spectrum, H2´´ and H3´´ showed correlations to the
quaternary carbon at 140.6 ppm; this carbon is assigned to C1´. In addition, these two protons
showed correlations to carbons C2´/C6´.
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Characterization of (Z)-2,2'-(1,2-diphenylethene-1,2-diyl)bis(benzofuran-3(2H)-one) (D2).
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13
1
1D H and C{1H}, 2D dqfCOSY, HSQC, and HMBC spectra of D2 are shown in Figs. S10–S14. H
chemical shift and multiplicity as well as 13C{1H} chemical shift data are summarized as follows: 1H NMR
(500 MHz, chloroform-d): δ 7.99 (d, J = 7.5 Hz, 2H), 7.62 (t, J = 8.2 Hz, 1H), 7.61 (d, J = 7.4 Hz, 1H),
7.42 (t, J = 7.5 Hz, 2H), 7.37 (t, J = 7.5 Hz, 1H), 7.33 (d, J = 8.2 Hz, 1H), 7.13 (t, J = 7.4 Hz, 1H). 13C{1H}
NMR (126 MHz, chloroform-d): δ 183.3 (s), 165.6 (s), 145.1 (s), 136.6 (d), 135.3 (s), 130.7 (d), 129.5 (d),
128.4 (d), 125.0 (s), 124.6 (d), 123.2 (d), 122.2 (s), 112.9 (d). High-resolution ESI–MS exact mass
calculated for C30H18O4 [M +Na]+ 465.1085, found 465.1086. Orange crystal, melting point = 163–
164 °C.
Analysis of 1H–1H correlations in the dqfCOSY spectrum (Fig. S12) as well as J-coupling
1
1
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patterns of the H peaks in the H spectrum (Fig. S10) revealed the assignments of the three H
peaks at 7.99, 7.42, and 7.37 ppm to five protons of the monosubstituted benzene ring. The signal
at 7.99 ppm (d, J = 7.5 Hz, 2H) is assigned to H2´ and H6´, which are equivalent, whereas the
signal at 7.42 ppm (t, J = 7.5 Hz, 2H) is assigned to H3´ and H5´ which are equivalent. Finally,
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the signal at 7.37 ppm (t, J = 7.5 Hz, 1H) is assigned to H4´. Second-order effects were seen for
the H4´ as well as H3´/H5´. Analysis of COSY correlations and J-coupling patterns also indicated
that the four protons at 7.62 (t, J = 8.2 Hz, 1H), 7.61 (d, J = 7.4 Hz, 1H), 7.33 (d, J = 8.2 Hz, 1H),
and 7.13 ppm (t, J = 7.4 Hz, 1H), respectively, belong to the 1,2-disubstituted benzene ring. An
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H6 triplet partially overlaps the H4 doublet in the H spectrum; however, these signals are
discernible in the 2D HSQC spectrum and are assigned to C4 and C6. In the 13C{1H} spectrum
(Fig. S11), the most downfield peak at 183.3 ppm is assigned to the carbonyl carbon C3. In the
HMBC spectrum (Fig. S14), the proton at 7.61 ppm showed a correlation to the carbonyl carbon
and is assigned to H4. Consequently, the other three protons of the 1,2-disubstituted benzene ring
at 7.62, 7.33, and 7.13 ppm can be assigned to H6, H7, and H5, respectively. All CH carbons can
be assigned from the HSQC (Fig. S13).
All other quaternary carbons can be assigned from the HMBC spectrum. Both H5 and H7
protons showed correlations to the carbon at 122.2 ppm; this carbon is assigned to C9 based on its
chemical shift and from the correlations through vicinal CH (3JCH) coupling. There is a correlation
of H4 and/or H6 protons with the carbon at 165.6 ppm; this carbon is assigned to C8. Due to the
overlap of protons H4 and H6, their individual correlations to carbon C8 were not resolved. A
weaker correlation between proton H7 and carbon C8 through geminal CH (2JCH) coupling was
also detected. In addition, the HMBC spectrum showed a strong correlation of protons H2´ and
H6´ with the carbon at 125.0 ppm; this carbon is assigned to C´´. Finally, the last carbon at 145.1
ppm, which did not show a correlation to any proton, is assigned to C2.
Characterization of (Z)-1,6-bis(2-hydroxyphenyl)-3,4-diphenylhex-3-ene-1,6-dione (I2).
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. H NMR (500 MHz, CDCl3): δ 12.14 (s, 1H, O–H), 7.5 (d, J = 8.3 Hz, 1H, H-2′), 7.39 (t, J = 7.8
Hz, 1H, H-4′), 7.35 (d, J = 7.3 Hz, 2H, H-2′′ + H-6′′), 7.30 (t, J = 7.7 Hz, 2H, H-3′′ + H-5′′), 7.22
(t, J = 7.3 Hz, 1H, H-4′′), 6.91 (d, J = 8.3 Hz, 1H, H-5′), 6.76 (t, J = 7.8 Hz, 1H, H-3′), 4.06 (s, 2H,
CH2). 13C{1H} NMR (126 MHz, CDCl3): δ 203.6 (C=O), 162.2 (C-5′a), 141.1 (C-1′′), 136.2 (C-
4′), 135.5 (C-3), 129.9 (C-2′), 128.6 (C-3′′ + C-5′′), 128.3 (C-2′′ + C-6′′), 127.5 (C-4′′), 119.3 (C-
2′a), 118.7 (C-3′), 118.4 (C-5′), 45.6 (CH2). High-resolution ESI–MS exact mass calculated for
C30H23O3 [M – H2O + H]+ 431.1675, found 431.1527.
We arrived at the structure of I2 by means of two-dimensional HMBC, COSY, and HSQC
NMR experiments (Fig. S17–S20). The structure of I2 is very similar to that of D1, except that
the two subunits are connected via a C=C bond for I1 instead of a single C–C bond for D1. NMR
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spectra of I2 are also similar to those of D1. In the 13C spectrum, the most deshielded carbon is
assigned to the carbonyl carbon C-1. In the HMBC spectrum (Fig. S15), an aromatic proton at 7.5
ppm shows a correlation to the carbonyl carbon; this proton is assigned as proton H2′. Protons
H2′ to H5′ and their directly attached carbons (C2′–C5′) can be assigned from the COSY (Fig.
S16) and the HSQC (Fig. S17) spectra, respectively. In the COSY spectrum, proton H2′ shows a
correlation with proton H3′, proton H3′ shows a correlation with proton H4′, and finally, proton
H4′ shows a correlation with proton H5′. Similarly, from the HSQC spectrum, the directly attached
carbons of protons H2′ to H5′ can be obtained. In the HMBC spectrum, protons H2′ and H4′ show
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3JCH correlations to carbons C4′ and C2′, respectively, whereas protons H3′ and H5′ show JCH
correlations to carbons C5′ and C3′, respectively. Moreover, data obtained from the HMBC
spectrum reveal that both H2′ and H4′ protons correlate with a carbon signal at 162.2 ppm. This
signal is assigned to carbon C5′a on the basis of its chemical shift and from the 3JCH correlations.
In addition, the HMBC spectrum shows that H3′ and H5′ protons are both correlated with a carbon
at 119.3 ppm; this carbon is assigned to C2′a.
We assigned the proton signal at 4.06 ppm to the methylene protons (H2). Methylene
proton H2 shows a correlation in the HMBC spectrum with the carbonyl carbon (C1); it also shows
a correlation with two other carbons at 135.5 and 141.1 ppm (Figs. S15 and S18). Carbons at
135.5 and 141.1 ppm are assigned to C3 and C1′′, respectively. In the HMBC spectrum, the two
protons at 7.35 ppm show correlation to carbon C3; these two protons are assigned to H2′′ and
H6′′; thus, protons H2′′ and H6′′ and their directly attached carbons (see HSQC spectrum in Fig.
S17) are equivalent. A triplet at 7.22 ppm in the proton spectrum shows a correlation to carbons
C2′′ and C6′′ in the HMBC spectrum (note that carbons C2′′ and C6′′ are equivalent); this triplet
is assigned to proton H4′′. In the proton spectrum, the triplet at 7.30 ppm (which integrates to two
protons) shows a correlation to carbon C1′′ in the HMBC spectrum; this triplet is assigned to
protons H3′′ and H5′′ which are equivalent.
Similarly, the proton signal at 12.14 ppm is assigned to the OH proton. This assignment is
supported by the fact that the proton does not show a correlation to any carbon in the HSQC
spectrum, implying that it is not directly bonded to a carbon. It shows three correlations in the
HMBC spectrum (Figs. S15 and S18), one to the quaternary carbon C5′a and two more to C2′a
and C5′. It must be noted that, due to the near overlap of carbons C5′ and C2′a, their individual
correlations to the OH proton are not resolved in the HMBC spectrum.
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Computational Analysis. Electronic structure calculations were performed with the aid
of the Gaussian (G16) package.46 We optimized geometries using B3LYP density functional47–49
with 6-31+G(d,p)50–53 basis set. The solvent environment was modeled with SMD-SCRF54 implicit
solvation model for acetonitrile as solvent ( = 35.688), included in all geometry optimizations.
Optimized geometries were confirmed as minima on the potential energy surface by vibrational
frequency calculations with no imaginary frequency. Transition states had with only one imaginary
frequency with a transition vector leading from reactant to the product. Transition states were
further validated using the intrinsic reaction coordinate (IRC) calculations. Thermal and entropy
contribution to the Gibbs free energy was calculated by the use of unscaled B3LYP frequencies
and rigid rotor/harmonic oscillator approximations at 298.15 K. For molecules with multiple
rotatable bonds, a conformational search was performed with the aid of the LowModeMD
module55 implemented in the molecular operating environment (MOE, version 2018.01) with
Amber2010:EHT force field.56 We further refined structures with energies lower than 5 kcal/mol
by performing geometry optimization at the B3LYP/6-31+G(d,p) level of theory in acetonitrile,
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and the lowest energy structure was used for further analysis.
X(sol) + ne(-sol) → Xn(s–ol)
E(sol)
o
For a reaction,
, the standard reduction potential,
is given by
∆G(*sol)
Eo(sol) = -
- SCE
n F
*
∆G(sol) = GX*,(sol) – GX* ,(sol) – Ge*,(g)
n +
where
is the standard free-energy change for a redox reaction
*
in acetonitrile and e (g) = 0.87 kcal/mol is the gas-phase free energy of the electron at 298.15 K
G
,
obtained from the literature.57 The faraday (F) is 23.06 kcal/(molV), and n is the number of
electrons, with SCE being the absolute potential of the standard calomel electrode (4.43 V).58 For
reactions involving proton-coupled electron transfer, the free energy of a proton in acetonitrile was
calculated from the relation
*
o
*
GH ,(sol) = GH ,(g) + ∆Gsolv,(sol) + ∆G1atm→1M
+
+
o
o
o
o
o
+
+
where
at 298.15 K is derived from
, with
GH ,(g) = H(g) – TS(g)
=
H(g)
G
H ,(g) = - 6.29 kcal/mol
o
*
1.48 kcal/mol,
= 26.05 cal/(molK),
= –260.5 kcal/mol is the solvation energy
S(g)
∆Gsolv,(acetonitrile)
of the proton taken from the literature,59 and
1atm→1M = 1.89 kcal/mol is the correction to the
∆G
free energy for changing from the standard state of 1 atm to 1 M.60
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Associated Content
The supporting information file is available free of charge on the ACS Publication website
at DOI: xx.xxxx./acs.joc.xxxxxxx
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Copies of 1H NMR and 13C NMR spectra for new compounds, X-ray diffraction data
(PDF), X-ray data for D1, I2 and D2 (CIF), Separation scheme, electrochemical studies
and, DFT computation results.
Author Information
Corresponding Author:
Email: mmubarak@indiana.edu; mmubarak@ju.edu.jo
ORCID
Seyyedamirhossein Hosseini: 0000-0002-3521-1062
Bishnu Thapa: 000-0003-3275-1426
Krishnan Raghavachari: 0000-0003-3275-1426
Dennis G. Peters: 0000-0002-3716-8355
Mohammad S. Mubarak: 0000-0002-9782-0835
Present Address
Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington,
IN, 47405.
Department of Chemistry, The University of Jordan, Amman 11942, Jordan
Notes
The authors declare no competing financial interest.
Acknowledgment
Krishnan Raghavachari acknowledges financial support from the National Science
Foundation (NSF), grant number CHE-1665427.
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