Reductive Coupling of Aromatic Aldehydes and Ketones under Electrochemical Conditions

Article abstract of DOI:10.1149/1945-7111/ab72ed

Reductive coupling of o-substituted carbonyl compounds and m-substituted carbonyl compounds by the direct transfer of electron to carbonyl group respectively gave 1-(4-(1-hydroxy-1-phenylethyl/methyl)phenyl)ethanones/methanones and 2,3-bis(3-substitutedph

Full text of DOI:10.1149/1945-7111/ab72ed

Journal of The Electrochemical
Society
Reductive Coupling of Aromatic Aldehydes and Ketones Under
Electrochemical Conditions
To cite this article: Toreshettahally R Swaroop et al 2020 J. Electrochem. Soc. 167 046504
View the article online for updates and enhancements.
This content was downloaded from IP address 134.115.5.47 on 19/02/2020 at 09:20

Journal of The Electrochemical Society, 2020 167 046504
1945-7111/2020/167(4)/046504/8/$40.00 © 2020 The Electrochemical Society (“ECS”). Published on behalf of ECS by IOP Publishing Limited
Reductive Coupling of Aromatic Aldehydes and Ketones Under
Electrochemical Conditions
Toreshettahally R Swaroop,1,2,z Zi-Qiang Wang,1 Qian-Yu Li,1 and Heng Shan Wang1,z
1State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University,
Guilin- 541004, People’s Republic of China
2Department of Studies in Organic Chemistry, University of Mysore, Manasagangothri, Mysuru- 570 006, Karnataka, India
Reductive coupling of o-substituted carbonyl compounds and m-substituted carbonyl compounds by the direct transfer of electron
to carbonyl group respectively gave 1-(4-(1-hydroxy-1-phenylethyl/methyl)phenyl)ethanones/methanones and 2,3-bis(3-substitu-
tedphenyl)butane/ethane-2,3-diols. 4-Methoxyacetophenone surprisingly gave 4-methoxybenzoic acid as oxidation product. Even
acetophenone conjugated with alkyne group afforded interesting reductive addition product. Finally, imine also furnished
reductively coupled diamino compound. Probable mechanisms for the formation of products is proposed.
© 2020 The Electrochemical Society (“ECS”). Published on behalf of ECS by IOP Publishing Limited. [DOI: 10.1149/1945-7111/
ab72ed]
Manuscript submitted November 8, 2019; revised manuscript received January 16, 2020. Published February 14, 2020.
Supplementary material for this article is available online
Electrochemistry involves addition or removal of electrons from
molecules or ions by the application of electrical potential. Its
application in organic chemistry has gained great attention and
termed as electro-synthesis. In electro-synthesis, potential is applied
across the electrodes with the flow of current through reaction
mixture. The reaction mixture contains some electrolytes to carry
electricity.1–10 Reactions are carried out at constant potential and
also at constant current.1–10 Various heterocyclic structures can be
constructed by employing electrochemical technique.9 Since elec-
tron is a mass-free reagent which avoids usage of equivalent amount
of reagents taken up in conventional synthesis, thus eliminates the
produce of waste. Interestingly, electron transfer to a functional
group changes its polarity, which is difficult to achieve by other
synthetic approaches.
Toluene was not a suitable solvent for this reaction (entry 7). A
mixture of acetonitrile and DMF furnished 2a in 33% yield (entry 8).
Use of ferrocene as an electron transfer reagent also did not improve
the yield (entry 9). With 30 mol% of the TBAI, yield of 2a was
slightly improved to 48% (entry 10). But, the reaction mixture was
intractable with 100 mol% of the TBAI (entry 11). Tetra-butyl
ammonium tetrafluroroborate in DMSO and ACN furnished product
2a in 30 and 35% yield respectively (entries 12 and 13). Using Pt as
cathode and RVC as anode, the desired product 2a was observed in
trace (entry 14). On increasing the current to 40 mA in DMSO, yield
of 2a was improved to 59% (entry 15). Further increase in current to
60 mA, slightly reduced the yield. (55%, entry 16). With 40 mA of
current in ACN and DMF, the product was formed in 37 and 30%
yield respectively (entries 17 and 18). Tetra-butylammonium bro-
mide gave the best result by yielding the required product in 72%
(entry 19). Tetra-butylammonium hexafluorophosphate, tetra-buty-
lammonium chloride and tetra-butylammonium tosylate gave pro-
duct 2a in 40, 50 and 37% yield respectively (entries 20, 21 and 22).
We extended the generality of the protocol for the synthesis
of 1-(4-(1-hydroxy-1-phenylethyl)phenyl)ethanone by taking other
o-substituted acetophenones (Table II). Thus, o-methoxyacetophe-
none and o-methylacetophenone bearing electron donating groups
furnished corresponding products 2b and 2c in 60 and 78% yield
respectively. o-Fluoroacetophenone containing electron withdrawing
group formed product 2d in 70% yield. A representative example for
α-substituted acetophenone—propiophenone also gave 1-(4-(1-hy-
droxy-1-phenylpropyl)phenyl)propan-1-one 2e in 82% yield. Later,
we elaborated the methodology for aldehyde substrates. In the same
way, electrolysis of benzaldehyde gave 4-(hydroxy(phenyl)methyl)
benzaldehyde 2f in 57% yield. o-Methoxy benzaldehyde, o-methyl
benzaldehyde and o-chloro benzaldehyde also underwent smooth
reaction to produce respective products 2g, 2h and 2i in 60, 65 and
51% yield respectively. Even o-disubstituted benzaldehyde such as
2-chloro-6-flurobenzaldehyde yielded desired product 2j in 55%.
Finally, o-nitroacetophenone and benzophenone on electrolysis
under the optimized reaction condition did not furnish any product
(2k and 2l) with complete recovery of substrate, probably because
the intermediate radical formed (blue in colour) was very stable
and was not much reactive to react further with another molecule
of it.
Electro-reductive formation of C–C bonds in organic halides,11–16
ketones,17–23 imines24–26 and imides27,28 are well known. Direct
transfer of electron from electrode to carbonyl group for the synthesis of
indolealkanones,29 isoindolinones,28 cyclohexanols,30 pyrrolizinones
and indolizinones26 are reported. Similarly, electron transfer to imines
for the synthesis of azetidine,31 pyrrolidinone and piperidinone32
derivatives are also reported.
Further, phenyl-carbonyl coupling reactions are induced by SmI2
and hexamethylphosphoramide (HMPA) are known (Scheme 1a).28
Besides, coupling of aromatic carbonyl compounds and imines are
induced by electro-generated SmI2 are also known (Scheme 1b).33
But these methods have severe drawbacks due to the use of
stoichiometric amounts of SmI2-HMPA28 and Sm as sacrificial
anode.33 To the best of our knowledge, phenyl-carbonyl coupling
reactions are not reported under electrochemical conditions. In
continuation of our efforts in organic synthesis,34–47 we report
here-in phenyl-carbonyl reductive coupling of o-substituted aromatic
carbonyl compounds (Scheme 1c) and carbonyl-carbonyl reductive
coupling of m-substituted carbonyl compounds (Scheme 1d).
Results and Discussion
Initially electrolysis of acetophenone 1a in DMSO using pla-
tinum as anode and cathode by passing 20 mA of current in the
presence of 15 mol% of tetra-butylammonium iodide (TBAI) gave
1-(4-(1-hydroxy-1-phenylethyl)phenyl)ethanone 2a in 45% yield as
an unexpected product (Scheme 2, entry 1, Table I). In the absence
of electricity, there was no progress in the reaction (entry 2). Only a
trace of product was observed in THF (entry 3). In methanol, 2a was
not observed (entry 4). In acetonitrile and DMF, the required product
was isolated in 46 and 35% yield respectively (entry 5 and 6).
Further, electrolysis of m-substituted acetophenones gave 2,3-bis
(3-substitutedphenyl)butane-2,3-diols as diastereomers (Table III,
diastereomeric ratios are given in parenthesis). Thus, m-methylace-
tophenone, m-methoxyacetophenone and m-fluoroacetophenone
gave 2,3-bis(3-methoxy/methyl/fluorophenyl)butane-2,3-diol 4a, 4b
and 4c in 85, 66 and 69% yield respectively. Similarly, m-substituted
aldehydes also furnished 2,3-bis(3-substitutedphenyl)ethane-2,3-
diols. Thus, m-methylbenzaldehyde and m-methoxybenzaldehyde
zE-mail: swarooptr@gmail.com; whengshan@163.com

Journal of The Electrochemical Society, 2020 167 046504
Scheme 1. Comparison of reported work and present work.
substituted with electron donating groups afforded 2,3-bis(3-methyl/
methoxyphenyl)ethane-2,3-diols 4d and 4e in 81 and 69% yield
respectively. Similarly, m-fluorobenzaldehyde and m-chlorobenzal-
dehyde substituted with electron withdrawing groups furnished 2,3-
bis(3-fluoro/chlorophenyl)ethane-2,3-diols 4f and 4g in 75 and 73%
yield respectively.
Surprisingly, electrolysis of 4-methoxyacetophenone 5 gave 4-
methoxy benzoic acid 7 in 63% yield via the formation of 2,3-bis(4-
methoxyphenyl)butane-2,3-diol 6, which was formed as diaster-
eomer in the ratio 1:8.1 (Scheme 3). Further, 1-(4-ethynylphenyl)
ethanone 8 under the aforementioned conditions furnished 1-(4-(3-
(4-ethynylphenyl)-3-hydroxybut-1-yn-1-yl)phenyl)ethanone in
56% yield (Scheme 4). On the other hand, electrolysis of N-(1-
phenylethylidene)aniline 10 furnished 2,3-diphenyl-2,3-phenylami-
nobutane 11 in 55% yield (Scheme 5).
Finally, cross coupling of o-methoxyacetophenone and o-methy-
lacetophenone under optimized reaction conditions furnished four
products 2b, 2c, 2m and 2n in 14%, 18%, 15% and 13% respectively
(Scheme 6). These products were inseparable in column chromato-
graphy and identified in LCMS.
9
The probable mechanism involves transfer of electron from
platinum cathode to carbonyl group of 1 to give radical anion 12
which undergo resonance stabilization to give radical anion 13. The
coupling of 13 with another molecule of 1 forms intermediate 14.
Hydrogen migration in 14 forms another radical anion 15, which is
stabilized by resonance to produce 16. Finally, oxidation of 16 at
anode gives product 2 (Scheme 7). On the other hand, similar
electron transfer to 3 gives radical anion 17, which undergo coupling
with carbonyl carbon of another molecule of 3 to form dianion 18,
oxidation of which generates biradical 19. Its protonation during
work-up gives product 4 (Scheme 8). The mechanism of formation
Scheme 2. Synthesis of 1-(4-(1-hydroxy-1-phenylethyl)phenyl)ethanone 2a.

Journal of The Electrochemical Society, 2020 167 046504
Table I. Optimization of reaction conditionsa).
Entry
Cathode/Anode/Current (mA)
Electrolyte(15 mol%)
Solvent
Time
% Yield of 2
1
2
3
4
5
6
7
8
Pt/Pt/20
Pt/Pt/00
Pt/Pt/20
Pt/Pt/20
Pt/Pt/20
Pt/Pt/20
Pt/Pt/20
Pt/Pt/20
Pt/Pt/20
Pt/Pt/20
Pt/Pt/20
Pt/Pt/20
Pt/Pt/20
Pt/RVC/20
Pt/Pt/40
Pt/Pt/60
Pt/Pt/40
Pt/Pt/40
Pt/Pt/40
Pt/Pt/40
Pt/Pt/40
Pt/Pt/40
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAIb)
TBAIc)
TBAId)
DMSO
DMSO
THF
MeOH
ACN
12 h
15 h
15 h
12 h
24 h
5 h
12 h
16 h
12 h
7
45%
0%
trace
0%
46%
35%
0%
33%
43%
48%
0%
30%
35%
trace
59%
55%
37%
30%
72%
40%
50%
37%
DMF
Toluene
ACN:DMF
DMSO
DMSO
DMSO
DMSO
ACN
DMSO
DMSO
DMSO
ACN
9
10
11
12
13
14
15
16
17
18
19
20
21
22
4 h
c)
n-Bu4NBF4
12 h
12 h
12 h
3 h
3 h
2.5 h
2 h
2.5 h
2.5 h
4 h
c)
n-Bu4NBF4
TBAIc)
TBAIc)
TBAIc)
TBAIc)
TBAIc)
DMF
n-Bu4NBrc)
DMSO
DMSO
DMSO
DMSO
c)
n-Bu4NPF6
n-Bu4NClc)
n-Bu4NOTsc)
6 h
a) Reaction conditions: 1a (0.5 mmol), Pt as anode and cathode; b) with 5 mol% Cp2Fe; c) 30 mol% was used; d) 100 mol% was used.
Scheme 3. Formation of 4-methoxybenzoic acid from 4-methoxy acetophenone.
Scheme 4. Synthesis of 1-(4-(3-(4-ethynylphenyl)-3-hydroxybut-1-yn-1-yl)phenyl)ethanone from 1-(4-ethynylphenyl)ethanone 9.
Scheme 5. Synthesis of 2,3-diphenyl-2,3-phenylaminobutane 11 from N-(1-phenylethylidene)aniline 10.

Journal of The Electrochemical Society, 2020 167 046504
Table II. Synthesis of 1-(4-(1-hydroxy-1-phenylethyl/methyl)phenyl)ethanones/methanones 2.
Scheme 6. Cross coupling of o-methoxyacetophenone and o-methylacetophenone.

Journal of The Electrochemical Society, 2020 167 046504
Table III. Synthesis of 2,3-bis(3-substitutedphenyl)butane/ethane-2,3-diols 4.
of 4-methoxybenzoic acid from 4-methoxycetophenone is not clear
at this stage.
To confirm the above-proposed radical mechanism, we con-
1a in the presence of butylated hydroxyl toluene (BHT), which did
not furnish the required product thus pointing out the radical
mechanism of this reductive coupling. To further shed light on the
mechanism and to know the redox pattern of reactants we performed
ducted a control experiment involving electrolysis of acetophenone
Scheme 7. Probable mechanism for the formation of 2.

Journal of The Electrochemical Society, 2020 167 046504
Scheme 8. Probable mechanism for the formation of 4.
cyclic voltammetric studies. Unfortunately, the reduction-oxidation
peaks were too weak to identify in the cyclic voltagram.
1-(2-Fluoro-4-(1-(2-fluorophenyl)-1-hydroxyethyl)phenyl)etha-
none (2d): Viscous liquid; H NMR (CDCl3, 400 MHz) δ 1.94 (s,
1
3H, CH3), 2.61 (s, 3H, CH3), 6.93–7.03 (m, 1H, Ar-H), 7.15–7.23
(m, 3H, Ar-H), 7.30–7.35 (m, 1H, Ar-H), 7.58–7.62 (t, J = 8.0 Hz,
1H, Ar-H), 7.80 (m, 1H, Ar-H). 13C NMR (CDCl3, 100 MHz) δ 29.3
(d, J = 1.0 Hz), 31.4 (d, J = 28.0 Hz), 74.7, 113.7 (d, J = 25.0 Hz),
116.4 (d, J = 22.0 Hz), 121.3 (d, J = 2.0 Hz), 123.6 (d, J = 3.0 Hz),
124.3 (d, J = 3.0 Hz), 127.2 (d, J = 4.0 Hz), 130.0 (d, J = 9.0 Hz),
130.6 (d, J = 55.0 Hz), 133.1 (d, J = 11.0 Hz), 155.5 (d, J = 8.0
Hz), 161.5 (d, J = 58.0 Hz), 163.5, 195.6 (d, J = 4.0 Hz). HRMS
(APPI+) m/z calcd for [C16H14F2O2]: 276.0962, found 276.0958.
Experimental
The starting materials were commercially available and were
used without further purification. Reactions were monitored by TLC
using precoated sheets with UV light for visualization. Products
were purified by preparative TLC. NMR spectra were recorded using
400 MHz Brucker spectrometer using the residual solvent peaks as
reference relative to TMS. High resolution mass spectra were
recorded using ESI-Q-TOF mass spectrometer.
1-(4-(1-Hydroxy-1-phenylpropyl)phenyl)propan-1-one
(2e):
Viscous liquid; 1H NMR (CDCl3, 400 MHz) δ 0.89 (t, J = 8.0
Hz, 3H, CH3), 1.20 (t, J = 8.0 Hz, 3H, CH3), 2.34 (q, J = 8.0 Hz,
2H, CH2), 2.97 (q, J = 8.0 Hz, 2H, CH2), 7.15 (s, 1H, OH),
7.23–7.26 (m, 1H, Ar-H), 7.31 (t, J = 8.0 Hz, 2H, Ar-H), 7.41 (d, J
= 8.0 Hz, 2H, Ar-H), 7.51 (d, J = 8.0 Hz, 2H, Ar-H), 7.90 (d, J =
8.0 Hz, 2H, Ar-H). 13C NMR (CDCl3, 100 MHz) δ 8.0, 8.3, 31.8,
34.3, 78.4, 126.1, 126.3, 127.2, 127.9, 128.4, 135.3, 146.4, 151.9,
200.6. HRMS (APPI+) m/z calcd for [C18H20O2]: 268.1463, found
268.1456.
General procedure for the synthesis of 2/4/7/9/11.—To a
solution of 0.5 mmol of 2/4/7/9/11 in DMSO (3 ml) in a three
neck round bottom flask fitted with platinum electrodes (1 cm × 1
cm) and passed a constant current of 15 mA was passed for 1–3 h
from an amperostate. Reaction was monitored by thin layer
chromatography. After the completion of the reaction, the reaction
mixture was diluted with ethyl acetate (30 ml), washed with brine
(20 ml). The aqueous layer was extracted with ethyl acetate (30 ml).
The combined ethyl acetate layer was washed with brine (20 ml).
The organic layer was evaporated under reduced pressure. The crude
products were purified by preparative TLC.
4-(Hydroxy(phenyl)methyl)benzaldehyde (2f): Viscous liquid; 1H
1
NMR (CDCl3, 400 MHz) δ H NMR (CDCl3, 400 MHz): 5.91 (s,
1H, CH), 7.26–7.37 (m, 5H, Ar-H),7.58 (d, J = 8.0 Hz, 2H, Ar-H),
7.86 (d, J = 8.0 Hz, 2H, Ar-H),9.99 (s, 1H, CHO) 13C NMR (CDCl3,
100 MHz) δ 76.0, 126.7, 126.9, 128.2, 128.8, 130.0, 135.7, 143.1,
150.3, 191.9. HRMS (APPI+) m/z calcd for [C14H12O2]: 212.0837,
found 212.0832.
4-(Hydroxy(2-methoxyphenyl)methyl)-2-methoxybenzaldehyde
(2g): Viscous liquid; 1H NMR (CDCl3, 400 MHz) δ 3.84 (s, 3H,
OCH3), 3.92 (s, 3H, OCH3), 6.1 (s, 1H, CH), 6.91–6.97 (m, 3H, Ar-
H), 7.17–7.26 (m, 2H, Ar-H), 7.30 (m, 1H, Ar-H), 7.76 (d, J = 8.0
Hz, 1H, Ar-H), 10.42 (s, 1H, CHO). 13C NMR (CDCl3, 100 MHz) δ
55.5, 55.6, 72.0, 109.5, 110.9, 118.8, 121.0, 123.7, 128.0, 128.4,
139.3, 131.0, 152.1, 156.7, 161.9, 189.6. HRMS (APPI+) m/z calcd
for [C16H16O4]: 272.1049, found 272.1044.
Spectral data.—1-(4-(1-Hydroxy-1-phenylethyl)phenyl)ethanone
(2a): Viscous liquid; 84 °C; 1H NMR (CDCl3, 400 MHz) δ 1.97 (s, 3H,
CH3), 2.58 (s, 3H, CH3), 7.27 (t, J = 8.0 Hz, 1H, Ar-H), 7.33 (t, J = 8.0
Hz, 2H, Ar-H), 7.41 (d, J = 8.0 Hz, 2H, Ar-H), 7.52 (d, J = 8.0 Hz,
2H, Ar-H), 7.90 (d, J = 8.0 Hz, 2H, Ar-H); 13C NMR (CDCl3, 100
MHz) δ 26.6, 30.6, 76.1, 125.8, 126.0, 127.3, 128.3, 128.4, 135.7,
147.2, 153.4, 197.9. HRMS (APPI+) m/z calcd for [C16H16O2]:
240.1150, found 240.1144.
1-(4-(1-Hydroxy-1-(2-methoxyphenyl)ethyl)-2-methoxyphenyl)
ethanone (2b): White solid; M. P. 84 °C. 1H NMR (CDCl3, 400
MHz) δ 1.82 (s, 3H, CH3), 2.59 (s, 3H, CH3), 3.62 (s, 3H, OCH3),
3.86 (s, 3H, OCH3), 6.69 (dd, J = 12.0 Hz, 4.0 Hz, 1H, Ar-H)，6.90
(d, J = 12.0 Hz, 1H, Ar-H),7.04 (t, J = 8.0 Hz, 1H, Ar-H), 7.13 (s,
1H, Ar-H), 7.32 (t, J = 8.0 Hz, 1H, Ar-H), 7.44 (d, J = 8.0 Hz, 1H,
Ar-H), 7.60 (d, J = 8.0 Hz, 1H, Ar-H). 13C NMR (CDCl3, 100 MHz)
δ 29.9, 31.9, 55.5, 55.6, 76.3, 108.2, 112.0, 117.3, 121.0, 126.2,
127.0, 129.2, 130.0, 134.1, 156.5, 156.9, 159.0, 199.5. HRMS (APPI
+) m/z calcd for [C18H20O4]: 300.1362, found 300.1357.
4-(Hydroxy(o-tolyl)methyl)-2-methylbenzaldehyde
(2h):
1
Viscous liquid; H NMR (CDCl3, 400 MHz) δ 2.31 (s, 3H, CH3),
2.65 (s, 3H, CH3), 6.04 (s, 1H, CH), 7.19–7.24 (m, 4H, Ar-H),
7.34–7.40 (m, 2H, Ar-H), 7.76 (m, 1H, Ar-H), 10.24 (s, 1H, CHO).
13C NMR (CDCl3, 100 MHz) δ 9.4, 19.7, 73.0, 124.7, 126.4, 126.8,
128.1, 130.1, 130.9, 132.3, 133.4, 135.6, 140.8, 140.9, 148.7, 192.3.
HRMS (APPI+) m/z calcd for [C16H16O2]: 240.1150, found
240.1144.
1-(4-(1-Hydroxy-1-(o-tolyl)ethyl)-2-methylphenyl)ethanone (2c):
Viscous liquid; 1H NMR (CDCl3, 400 MHz) δ 1.91 (s, 3H, CH3),
2.01 (s, 3H, CH3), 2.49 (s, 3H, CH3), 2.55 (s, 3H, CH3), 7.11–7.26 (m,
5H, Ar-H), 7.62–7.66 (m, 2H, Ar-H). 13C NMR (CDCl3, 100 MHz) δ
21.4, 22.0, 29.5, 32.6, 76.7, 122.7, 125.5, 126.0, 128.0, 128.9, 129.7,
132.6, 135.7, 137.4, 138.8, 143.8, 151.7, 201.3. HRMS (APPI+) m/z
calcd for [C18H20O2]: 268.1463, found 268.1459.
2-Chloro-4-((2-chlorophenyl)(hydroxy)methyl)benzaldehyde
(2i): Viscous liquid; 1H NMR (CDCl3, 400 MHz) δ 6.28 (s, 1H, CH),
7.27–7.29 (m, 2H, Ar-H), 7.29–7.32 (m, 2H, Ar-H), 7.38–7.40 (m,
1H, Ar-H), 7.56 (d, J = 1.0 Hz, 1H, Ar-H), 7.88 (d, J = 8.0 Hz, 1H,
Ar-H), 10.44 (s, 1H, CHO). 13C NMR (CDCl3, 100 MHz) δ 71.6,

Journal of The Electrochemical Society, 2020 167 046504
125.6, 127.6, 128.3, 128.6, 129.5, 129.6, 129.9, 131.7, 132.5, 138.1,
139.8, 150.1, 189.4. HRMS (APPI+) m/z calcd for [C14H10Cl2O2]:
280.058, found 280.00054.
2.57 (s, 4H, OH), 3.79 (s, 6H, OCH3), 3.80 (s, 6H, OCH3), 6.75–6.78
(m, 8H, Ar-H), 7.09–7.12 (m, 8H, Ar-H). 13C NMR (CDCl3, 100
MHz) δ 25.0, 25.2, 55.2, 78.5, 78.7, 112.4, 112.6, 112.1, 128.6,
135.8, 136.1, 158.4, 158.5. HRMS (APPI+) m/z calcd for
[C18H22O4]: 302.1518, found 302.1514.
2-Chloro-4-((2-chloro-6-fluorophenyl)(hydroxy)methyl)-6-fluor-
1
obenzaldehyde (2j): Viscous liquid; H NMR (CDCl3, 400 MHz) δ
1
3.00 (s, 1H, OH), 6.38 (s, 1H, CH), 7.03–7.08 (m, 2H, Ar-H),
7.30–7.31 (m, 3H, Ar-H), 10.42 (s, 1H, CHO). 13C NMR (CDCl3,
100 MHz) δ 186.6, 164.66 and 162.02 (d, J = 264.0 Hz), 162.7 and
160.2 (d, J = 250.0 Hz), 150.9 (d, J = 9.0 Hz), 137.2 (d, J = 4.0
Hz), 134.0 (d, J = 6.0 Hz), 130.9 (d, J = 10.0 Hz), 127.2 (d, J =
14.0 Hz), 126.3 (d, J = 4.0 Hz), 123.6 (d, J = 2.0 Hz), 120.6 (d, J =
9.0 Hz), 115.4 (d, J = 22.0 Hz), 112.9 (d, J = 23.0 Hz), 68.8. HRMS
(APPI+) m/z calcd for [C14H8Cl2F2O2]: 315.9869, found 315.9865.
2,3-Di-m-tolylbutane-2,3-diol (4a): Viscous liquid; 1H NMR
(CDCl3, 400 MHz) δ 1.44 (s, 6H, 2CH3), 1.53 (s, 6H, 2CH3), 2.26
(s, 6H, 2CH3), 2.28 (s, 6H, 2CH3), 2.60 (4H, OH), 6.97–7.14 (m,
16H, Ar-H). 13C NMR (CDCl3, 100 MHz) δ 21.6, 25.0, 25.1, 78.7,
78.9, 124.1, 124.6, 127.0, 127.2, 127.6, 127.8, 127.9, 128.3, 136.5,
136.7, 143.4, 143.7. HRMS (APPI+) m/z calcd for [C18H22O2]:
270.1620, found 270.1617.
2,3-Bis(3-methoxyphenyl)butane-2,3-diol (4b): Viscous liquid;
1H NMR (CDCl3, 400 MHz) δ 1.5 (s, 6H, 2CH3), 1.56 (s, 6H,
2CH3), 3.69 (s, 6H, 2OCH3), 7.72 (s, 6H, 2OCH3), 6.78–6.81 (m,
12H, Ar-H), 7.14–7.25 (m, 4H, Ar-H). 13C NMR (CDCl3, 100 MHz)
δ 25.0, 25.2, 55.1, 78.6, 78.9, 112.5, 112.6, 113.0, 133.4, 119.4,
114.0, 128.0, 128.2, 145.2, 145.6, 158.6, 158.8. HRMS (APPI+) m/z
calcd for [C18H22O4]: 302.1518, found 302.1514.
4-Methoxy benzoic acid (7): White solid; H NMR (CDCl3, 400
MHz) δ 3.88 (s, 3H, OCH3), 6.94 (d, J = 8.0 Hz, 2H, Ar-H), 8.07 (d,
J = 8.0 Hz, 2H, Ar-H). 13C NMR (CDCl3, 100 MHz) δ 55.5, 113.8,
121.7, 132.4, 164.1, 171.5. HRMS (APPI+) m/z calcd for
[C18H22O4]: 152.0473, found 152.0470.
1-(4-(3-(4-Ethynylphenyl)-3-hydroxybut-1-yn-1-yl)phenyl)etha-
none (9): Viscous liquid; 1H NMR (CDCl3, 400 MHz) δ 1.78 (s, 3H,
CH3), 2.59 (s, 3H, CH3), 3.08 (s, 1H, CH), 7.44–7.49 (m, 6H, Ar-H),
7.90 (d, J = 8.0 Hz, 2H, Ar-H). 13C NMR (CDCl3, 100 MHz) δ 26.6,
29.7, 74.6, 77.2, 77.2, 83.4, 124.9, 125.3, 126.7, 128.5, 128.8, 132.2,
136.2, 138.6, 146.8, 197.6. HRMS (APPI+) m/z calcd for
[C20H16O2]: 288.1150, found 288.1144.
2,3-Diphenyl-2,3-phenylaminobutane (11): Viscous liquid; 1H
NMR (CDCl3, 400 MHz) δ 1.51 (s, 6H, 2CH3), 1.52 (s, 6H, 2CH3),
4.06 (s, 4H, NH), 6.36–6.50 (m, 4H, Ar-H), 6.51 (d, J = 8.0 Hz, 4H,
Ar-H), 6.64 (t, J = 8.0Hz, 2H, Ar-H), 7.06–7.14 (m, 8H, Ar-H),
7.15–7.24 (m, 6H, Ar-H), 7.25–7.38 (m, 16H, Ar-H); 13C NMR
(CDCl3, 100 MHz) δ 24.9, 25.0, 53.5, 53.5, 108.9, 113.3, 114.9,
117.3, 125.8, 125.9, 128.6, 128.7, 129.1, 131.8, 144.6, 145.2, 146.2,
147.3. HRMS (APPI+) m/z calcd for [C28H28N2]: 392.2252, found
392.2247.
2,3-Bis(3-fluorophenyl)butane-2,3-diol (4c): Viscous liquid; 1H
NMR (CDCl3, 400 MHz) δ 1.50 (s, 6H, CH3), 1.54 (s, 6H, CH3),
2.27 (s, 2H, OH), 2.60 (s, 2H, OH), 6.87–7.16 (m, 12H, Ar-H),
7.17–7.26 (m, 4H, Ar-H). 13C NMR (CDCl3, 100 MHz) δ 24.8, 25.1,
78.2, 78.5, 113.7, 113.9, 114.2, 114.3, 114.5, 114.7, 123.0 (d, J =
8.0 Hz), 128.7 (d, J = 8.0 Hz), 128.5, 146.1 (d, J = 7.0 Hz), 146.6
(d, J = 4.0 Hz), 161.0 (d, J = 14.0 Hz), 163.4 (d, J = 14.0 Hz).
HRMS (APPI+) m/z calcd for [C16H16F2O2]: 278.1118, found
278.1115.
Conclusions
In conclusion, we have reported electro-reductive phenyl-car-
bonyl coupling of o-substituted aromatic carbonyl compounds for
the synthesis of 1-(4-(1-hydroxy-1-phenylethyl/methyl)phenyl)etha-
nones/methanones and reductive carbonyl-carbonyl coupling of m-
substituted carbonyl compounds for the synthesis of 2,3-bis(3-
substitutedphenyl)butane/ethane-2,3-diols. The present method
avoids the use of stoichiometric amount of Sm and its compounds,
and HMPA. Further, electrolysis of p-methoxy acetophenone
surprisingly gave p-methoxy benzoic acid. Even conjugation ex-
tended system also furnished corresponding reductive addition
product. Finally, imine also formed diamino compound as reductive
coupling product. Thus, the present method describes an Umpolung
reductive coupling of carbonyl compounds and imines. Radical
mechanisms for the formation of products is proposed.
1,2-Di-m-tolylethane-1,2-diol (4d): Viscous liquid; 1H NMR
(CDCl3, 400 MHz) δ 2.25 (s, 6H, 2CH3), 2.30 (s, 6H, 2CH3), 2.69
(s, 4H, OH), 4.56 (s, 2H, 2CH), 4.65 (s, 2H, 2CH), 6.84 (d, J = 8.0
Hz, 2H, Ar-H), 6.92 (s, 2H, Ar-H), 7.00–7.10 (s, 10H, Ar-H), 7.18 (t,
J = 8.0 Hz, 2H, Ar-H). 13C NMR (CDCl3, 100 MHz) δ 21.4, 21.5,
78.2, 78.8, 124.1, 124.3, 127.6, 127.9, 130.0, 128.2, 128.6, 128.9,
137.7, 137.9, 140.0, 140.0. HRMS (APPI+) m/z calcd for
[C16H18O2]: 242.1307, found 242.1304.
1,2-Bis(3-methoxyphenyl)ethane-1,2-diol (4e): Viscous liquid;
1H NMR (CDCl3, 400 MHz) δ 3.72 (s, 6H, 2OCH3), 3.74 (s, 6H,
2OCH3), 4.67 (s, 2H, 2CH), 4.78 (s, 2H, 2CH), 6.71–6.88 (m, 12H,
ArH), 7.15 (t, J = 8.0 Hz, 2H, Ar-H), 7.22–7.26 (m, 2H, Ar-H). 13C
NMR (CDCl3, 100 MHz) δ 55.2, 55.2, 78.0, 78.9, 112.2, 112.3,
113.7, 114.0, 119.2, 119.4, 129.2, 129.3, 141.4, 141.6, 159.5, 159.6.
HRMS (APPI+) m/z calcd for [C16H18O4]: 274.1205, found
274.1200.
Acknowledgments
TRS thank Government of China for postdoctoral fellowship.
References
1. I. Tabakovic, “Anodic synthesis of heterocyclic compounds.” Top. Curr. Chem., 87,
185 (1997).
2. H. Lund, O. E. Hammerich, and M. Dekker, in Organic Electrochemistry (Elsevier,
New York) 4th ed., p. 1393 (2001).
1,2-Bis(3-fluorophenyl)ethane-1,2-diol (4f): Viscous liquid; 1H
NMR (CDCl3, 400 MHz) δ 3.41 (s, 4H, OH), 4.58 (s, 2H, CH), 4.79
(s, 2H, CH), 6.75–6.96 (m,12H, Ar-H), 7.12–7.25 (m, 4H, Ar-H). 13C
NMR (CDCl3, 100 MHz) δ 77.1 (d, J = 1.0 Hz), 78.4 (d, J = 2.0
Hz), 113.8 (d, J = 14.0. Hz), 114.0 (d, J = 14.0 Hz),114.9 (d, J =
5.0 Hz), 115.1 (d, J = 5.0 Hz), 112.6 (t, J = 3.0 Hz), 129.6 (d, J =
8.0 Hz), 129.7 (d, J = 9.0 Hz),141.9 (d, J = 7.0 Hz), 142.1 (d, J =
7.0 Hz), 163.9, 161.4. HRMS (APPI+) m/z calcd for [C14H12F2O2]:
250.0805, found 250.0801.
3. C. Moinet, A. J. Bard, and M. Stratmann, in Encyclopedia of Electrochemistry
(Wiley-VCH, Weinheim) p. 341 (2004).
4. J. B. Sperry and D. L. Wright, Chem. Soc. Rev., 605, 35 (2006).
5. J. Yoshida, K. Kataoka, R. Horcajada, and A. Nagaki, Chem. Rev., 108, 2265
(2008).
6. R. Francke and R. D. Little, Chem. Soc. Rev., 43, 2492 (2014).
7. R. Francke, Beilstein J. Org. Chem., 10, 2858 (2014).
8. M. Yan, Y. Kawamata, and P. S. Baran, Chem. Rev., 117, 13230 (2017).
9. Y. Jiang, K. Xu, and C. Zeng, Chem. Rev., 118, 4485 (2018).
10. K. Liu, C. Song, and A. Lei, Org. Biomol. Chem., 16, 2375 (2018).
11. A. P. Esteves, D. M. Goken, L. J. Klein, M. A. Lemos, M. J. Medeiros, and
D. G. Peters, J. Org. Chem., 68, 1024 (2003).
1
1,2-Bis(3-chlorophenyl)ethane-1,2-diol (4g): Viscous liquid; H
́
́
́
12. J. C. Mendonca̧ Cavalcanti, M. O. Fonseca Goulart, E. Leonel, and J.-Y. Nedelec,
NMR (CDCl3, 400 MHz) δ 2.56 (s, 4H, OH), 4.62 (d, J = 8.0 Hz,
2H, Ar-H), 4.79 (d, J = 8.0 Hz, 2H, Ar-H), 7.17–7.26 (m, 12H, Ar-
H). 13C NMR (CDCl3, 100 MHz) δ 78.3, 125.2, 125.3, 127.0, 127.2,
128.3, 128.3, 129.4, 129.4, 134.2, 134.3, 141.6, 141.7. HRMS (APPI
+) m/z calcd for [C14H12Cl2O2]: 282.0214, found 282.0211.
2,3-Bis(4-methoxyphenyl)butane-2,3-diol (6): Viscous liquid; 1H
NMR (CDCl3, 400 MHz) δ 1.46 (s, 6H, CH3), 1.55 (s, 6H, CH3),
Tetrahedron Lett., 43, 6343 (2002).
13. J. M. Huang, X. X. Wang, and Y. Dong, Angew. Chem. Int. Ed., 50, 924 (2011).
14. K. Mitsudo, Y. Nakagawa, J. I. Mizukawa, H. Tanaka, R. Akaba, T. Okada, and
S. Suga, Electrochim. Acta, 82, 444 (2012).
15. H. Senboku, J.–Y. Michinishi, and S. Hara, Synlett, 2011, 1567 (2011).
16. E. Dunach, A. P. Esteves, M. J. Medeiros, D. Pletcher, and S. J. Olivero,
̃
Electroanal. Chem., 566, 39 (2004).
17. A. Katayama, H. Senboku, and S. Hara, Tetrahedron, 72, 4626 (2016).

Journal of The Electrochemical Society, 2020 167 046504
18. F. LeStrat, J. A. Murphy, and M. Hughes, Org. Lett., 4, 2735 (2002).
36. X. Wang, S.-Y. Li, Y.-M. Pan, H.-S. Wang, H. Liang, Z.-F. Chen, and X.-H. Qin,
19. T. Shono and M. Mitani, J. Am. Chem. Soc., 93, 5284 (1971).
20. T. Shono, I. Nishiguchi, H. Ohmizu, and M. Mitani, J. Am. Chem. Soc., 100, 545
(1978).
Org. Lett., 16, 580 (2014).
37. H.-Z. Xie, Q. Gao, Y. Liang, H.-S. Wang, and Y.-M. Pan, Green Chem., 16, 2132
(2014).
21. T. Shono, I. Nishiguchi, and H. Omizu, Chem. Lett., 5, 1233 (1976).
22. T. Shono, N. Kise, T. Suzumoto, and T. Morimoto, J. Am. Chem. Soc., 108, 4676
(1986).
38. J.-L. Li, Y.-C. Wang, W.-Z. Li, H.-S. Wang, D.-L. Mo, and Y.-M. Pan, Chem.
Commun., 51, 17772 (2015).
39. J.-L. Li, W.-Z. Li, Y.-C. Wang, Q. Ren, H.-S. Wang, and Y.-M. Pan, Chem.
Commun., 52, 10028 (2016).
23. N. Kise, T. Suzumoto, and T. Shono, J. Org. Chem., 59, 1407 (1994).
̈
̈
24. R. Gorny, H. J. Schafer, and R. Frohlich, Angew. Chem. Int. Ed. Engl., 34, 2007 (1995).
25. S. Goda, K. Yamada, Y. Yamamoto, H. Maekawa, and I. Nishiguchi,
J. Electroanal. Chem., 545, 129 (2003).
40. Y.-Y. Xie, Y.-C. Wang, Y. He, D.-C. Hu, H.-S. Wang, and Y.-M. Pan, Green
Chem., 19, 656 (2017).
41. F.-H. Cui, J. Chen, Z.-Y. Mo, S.-X. Su, Y.-Y. Chen, X.-L. Ma, H.-T. Tang,
H.-S. Wang, Y.-M. Pan, and Y.-L. Xu, Org. Lett., 20, 925 (2018).
42. W. Tong, W.-H. Li, Y. He, Z.-Y. Mo, H.-T. Tang, H.-S. Wang, and Y.-M. Pan, Org.
Lett., 20, 2494 (2018).
26. N. Kise, T. Mano, and T. Sakurai, Org. Lett., 200810, 4617 (2008).
27. N. Kise, J. Org. Chem., 69, 2147 (2004).
28. N. Kise, H. Ozaki, N. Moriyama, Y. Kitagishi, and N. Ueda, J. Am. Chem. Soc.,
125, 11591 (2003).
43. Q. H. Teng, X. J. Peng, Z. Y. Mo, Y. L. Xu, H. T. Tang, H. S. Wang, H. B. Sun, and
29. T. Shono, N. Kise, N. Kunimi, and R. Nomura, Chem. Lett., 20, 2191 (1991).
30. N. Kise, S. Isemoto, and T. Sakurai, Org. Lett., 11, 4902 (2009).
31. J. D. Parrish and R. D. Little, Tetrahedron Lett., 42, 7767 (2001).
32. N. Kise, K. Fukazawa, and T. Sakurai, Tetrahedron Lett., 51, 5767 (2010).
33. N. Kise, K. Ohya, K. Arimoto, Y. Yamashita, Y. Hirano, T. Ono, and N. Ueda,
J. Org. Chem., 69, 7710 (2004).
34. J. S. Shiue, M. H. Lin, and J. M. Fang, J. Org. Chem., 62, 4643 (1997).
35. K. Sahloul, L. Sun, A. Requet, Y. Chahine, and M. Mellah, Chem. Eur. J., 18,
11205 (2012).
Y.-M. Pan, Green Chem., 20, 2007 (2018).
44. Z.-Y. Mo, T. R. Swaroop, W. Tong, Y.-Z. Zhang, H.-T. Tang, Y.-M. Pan,
H.-B. Sun, and Z.-F. Chen, Green Chem., 20, 4428 (2018).
45. Q.-Y. Li, T. R. Swaroop, C. Hou, Z.-Q. Wang, Y.-M. Pan, and H.-T. Tang, Adv.
Synth. Catal., 361, 1761 (2019).
46. T. R. Dukanya, R. Swaroop, Shobith, K. S. Rangappa, and Basappa, Synopen, 3, 71
(2019).
47. K. R. Kiran, T. R. Swaroop, K. P. Sukrutha, J. B. Shruthi, S. M. Anil,
K. S. Rangappa, and M. P. Sadashiva, Synthesis, 51, 4205 (2019).