Mechanism of electrochemical reduction of 5-thio derivatives of 2(5H)-furanone

Article abstract of DOI:10.1007/s11172-019-2387-5

The anionoid elimination of the substituent from position 5 of the lactone ring is the predominant pathway of electrochemical reduction of 5-arylsulfanyl- and 5-arylsulfonyl-3,4-dichloro-2(5H)-furanones in acetonitrile. The contribution of the competing elimination of the chloride ion increases on going to 3,4-dichloro-5-ethylsulfanyl-2(5H)-furanone. An experimental criterion based on the morphology of cyclic voltammograms was proposed for identification of a particular pathway of electroreduction of 2(5H)-furanone derivatives.

Full text of DOI:10.1007/s11172-019-2387-5

Russian Chemical Bulletin, International Edition, Vol. 68, No. 2, pp. 313—327, February, 2019
313
Mechanism of electrochemical reduction of 5-thio derivatives of 2(5H)-furanone*
L. Z. Latypova,а G. A. Chmutova,а A. R. Kurbangalieva,а and V. V. Yanilkinb
аA. M. Butlerov Institute of Chemistry, Kazan Federal University,
18 ul. Kremlevskaya, 420008 Kazan, Russian Federation.
Fax: +7 (843) 238 7901. E-mail: llatypov@kpfu.ru
bA. E. Arbuzov Institute of Organic and Physical Chemistry,
Federal Research Center "Kazan Scientific Center of the Russian Academy of Sciences",
8 ul. Akad. Arbuzova, 420088 Kazan, Russian Federation.
Fax: +7 (843) 273 2253
The anionoid elimination of the substituent from position 5 of the lactone ring is the predo-
minant pathway of electrochemical reduction of 5-arylsulfanyl- and 5-arylsulfonyl-3,4-dichloro-
2(5H)-furanones in acetonitrile. The contribution of the competing elimination of the chloride
ion increases on going to 3,4-dichloro-5-ethylsulfanyl-2(5H)-furanone. An experimental
criterion based on the morphology of cyclic voltammograms was proposed for identification of
a particular pathway of electroreduction of 2(5H)-furanone derivatives.
Key words: 2(5H)-furanones, thioethers, sulfones, mucochloric acid, electrochemical reduc-
tion, voltammetry, quantum chemical calculations.
Polyfunctional unsaturated heterocyclic derivatives
attract considerable attention as promising compounds for
solving both fundamental and practical problems. One of
these heterocycles is a readily accessible and a highly reac-
tive γ-lactone, 3,4-dichloro-5-hydroxy-2(5H)-furanone
(mucochloric acid).1—4 The unsaturated γ-lactone moiety
is encountered in many biologically active natural products
possessing antifungal, antibacterial, anti-inflammatory,
and antitumor properties4—9 and attracts considerable
attention of researchers.
an exceptional regioselectivity of chlorine substitution by
the hydrogen atom in position 4 of the lactone ring giving
5-alkoxy-3-chloro-2(5H)-furanones (Scheme 1).
Scheme 1
This work continues research into the synthesis, struc-
tures, and properties of sulfur-containing 2(5H)-furanone
derivatives. Previously, we identified conditions for selec-
tive introduction of SR-substituents into positions 3, 4,
and 5 of the lactone ring; this allowed the synthesis of
a broad range of thioethers, bis-thioethers, and sulfur
heterocycles of different structural types from mucochloric
acid.3,10—14 Also, we studied chemical and electrochemi-
cal oxidation of furanone thioethers and developed efficient
protocols for the synthesis of sulfones and sulfoxides.15—18
Scanty data on the chemical reduction of 3,4-dihalo-
5-hydroxy derivatives of 2(5H)-furanones are available
from the literature.19—23 The electrochemical reduction
(ECR) of 2(5H)-furanone derivatives has been studied
only in relation to mucochloric acid and its 5-alkoxy de-
rivatives.24,25 It is also noteworthy that for the ECR of
5-alkoxy-3,4-dichloro-2(5H)-furanones 1—4, we found25
R = Me (1), Et (2), Pri (3), CH2CH2Cl (4)
ECR is electrochemical reduction.
In this work, we intended to investigate the ECR of
various 2(5H)-furanone thio derivatives that we obtained
previously, including compounds 6—12 containing sulf-
anyl and sulfonyl groups in position 5 of the lactone ring.
R = 4-MeC6H4 (6, 10), 4-ClC6H4 (7, 11 ), 4-BrC6H4 (8, 12), Et (9)
Along with solution of synthetic challenges, we at-
tempted to gain insight into the mechanisms of the studied
* Dedicated to Academician of the Russian Academy of Sciences
A. I. Konovalov on the occasion of his 85th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 0313—0327, February, 2019.
1066-5285/19/6802-0313 © 2019 Springer Science+Business Media, Inc.

314
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
Latypova et al.
following conditions: injector temperature of 280 C and split
ratio of 1 : 50. The temperature was programmed from 120 C
reactions. We used the same investigation algorithm as was
applied to the ECR of 5-alkoxy derivatives 1—4,25 in
particular, quantum chemical and voltammetric studies
and preparative electrolysis under conditions similar to
those used for the ECR of 5-alkoxy derivatives 1—4 (aceto-
nitrile as the solvent, Bu4NBF4 and Et4NBF4 as support-
ing electrolytes, and acetic acid as the proton donor).
(1 min) to 280 C (15 min) with a heating rate of 10 C min–1
.
The carrier gas flow rate through the column was 1 mL min–1
.
The temperature of the data exchange unit with the mass spectro-
meter was 280 C. The sample volume was 1 L.
The preparative ECR of compounds 6 and 9 was carried out
in a divided (porous glass, cellulose) electrolytic cell in the gal-
vanostatic mode at controlled potentials of the first reduction
peak under inert gas (argon) atmosphere at room temperature
(Т = 295 К) using a B5-50 direct current source. During elec-
trolysis, the solution was magnetically stirred and the potential
was monitored with a PI-50-1 potentiostat. Lead (S = 18.4 cm2)
or glassy carbon cloth (S = 15.8 cm2) cylinders served as the
cathode, a platinum helix was used as the anode, and Ag/AgNO3
(0.01 mol L–1) in МeCN was the reference electrode; Et4NBF4
and Et4NClO4 served as supporting electrolytes (0.05 mol L–1).
The reduction of 3,4-dichloro-5-[(4-methylphenyl)sulfanyl]-
2(5H)-furanone (6) was carried out using two different electrodes,
a GC electrode (experiment A) and a lead electrode (experiment B).
Experiment A. The working solution (total volume of 30 mL)
was prepared by dissolution of furanone 6 (0.86 g, 3.1 mmol),
Experimental
Cyclic voltammograms (CV curves) were measured on
a PI-50-1 potentiostat using an N307/2 two-coordinate re-
corder. The working electrodes included a glassy carbon (GC)
disc electrode (d = 3.4 mm) and a copper disc electrode
(d = 2 mm) pressed into a fluoroplastic; a lead disc electrode
(d = 3 mm), a silver disc electrode (d = 0.8 mm), and a platinum
disc electrode (d = 1.2 mm) sealed in glass; and a mercury disc
electrode fabricated by mercury deposition on platinum
(d = 2 mm) pressed into a fluoroplastic. Prior to each measure-
ment, the electrodes were mechanically polished. The potential
sweep rates were  = 100 and 200 mV s–1. The potentials were
measured and presented versus an Ag/AgNO3 silver reference
electrode (0.01 mol L–1) in acetonitrile; and a platinum wire
served as an auxiliary electrode. Oxygen dissolved in the sup-
porting electrolyte was removed by bubbling argon through the
solution. All measurements were carried out at 295 К.
Organic solvents were purified and dried by standard proce-
dures.26 The supporting salts Et4NBF4, Bu4NBF4, Et4NClO4,
NaClO4, and LiClO4 (Aldrich) were used as received. Com-
mercially available 3,4-dichloro-5-hydroxy-2(5H)-furanone
(mucochloric acid, 5) (CJSC Vekton) was recrystallized from
water, m.p. 127 C (see Ref. 27). 3,4-Dichloro-5-[(4-methyl-
phenyl)sulfanyl]-2(5H)-furanone11 (6), 3,4-dichloro-5-[(4-
chlorophenyl)sulfanyl]-2(5H)-furanone11 (7), 5-[(4-bromo-
phenyl)sulfanyl]-3,4-dichloro-2(5H)-furanone11 (8), 3,4-di-
chloro-5-ethylsulfanyl-2(5H)-furanone28 (9), 3,4-dichloro-5-
[(4-methylphenyl)sulfonyl]-2(5H)-furanone16 (10), 3,4-di-
chloro-5-[(4-chlorophenyl)sulfonyl]-2(5H)-furanone16 (11), and
5-[(4-bromophenyl)sulfonyl]-3,4-dichloro-2(5H)-furanone16
(12) were synthesized by known procedures.
NMR spectra were recorded on a Bruker Avance III-400
instrument operating at 400.17 (1H) and 100.62 MHz (13C) at
25 C for CDCl3 solutions. The chemical shifts were referred to
the residual proton signals in CDCl3. TLC analysis was carried
out on Kieselgel 60 F254 plates (Merck, Germany) using 1 : 9 and
1 : 15 (v/v) acetone—toluene mixtures for elution. Column
chromatography was carried out on silica gel 60 (Fluka,
70—230 mesh, 0.063—0.200 mm). Melting points were measured
on an OptiMelt Stanford Research Systems MPA100 automated
instrument and not corrected.
Gas chromatography–mass spectrometry study was con-
ducted on a DFS Thermo Electron Corporation instrument
(Germany). Electron impact ionization was used, the energy of
ionizing electrons was 70 eV, and the ion source temperature was
280 C. A 30-m long DB-5MS capillary column (Agilent) of
diameter 0.254 mm was used. Helium served as the carrier gas.
The mass spectral data were processed using the Xcalibur pro-
gram. Prior to injection, the samples were diluted to a concentra-
tion of 1•10–3 mol L–1 with chromatographically pure acetone
or dichloroethane. The chromatograms were measured under the
Et4NBF4 (0.38 g, 1.8 mmol), and AcOH (ρ = 1.062 g mL–1
;
0.71 mL, 12.5 mmol) in МeCN. Electrolysis was carried out on
a GC electrode (S = 15.8 cm2) at I = 50 mA for 4 h 40 min
(Q = 2.8 F mol–1). For neutralization of the acid formed during
electrolysis, Et4NOH (0.6 mL) was added into the anode com-
partment. After electrolysis, the reaction mixture was concen-
trated under reduced pressure up to complete removal of МeCN.
According to 1H NMR data, the residue contained furanones 13
and 14 in 0.8 : 1 ratio and disulfide 15, which were separated by
column chromatography with gradual increase in the eluent
polarity (acetone—toluene gradient, 1 : 151 : 2). Three major
fractions were evaporated to dryness and the residues were ad-
ditionally purified and analyzed.
The yellow solid residue of the fraction with Rf 0.77 (acet-
one—toluene, 1 : 15) contained 1,2-di(p-tolyl)disulfane (15).
Yield 8%, colorless crystals, m.p. 43 C (from hexane) (cf. Ref. 29:
m.p. 43–44 C). 1H NMR, δ: 2.32 (s, 6 H, CH3); 7.10, 7.38
(8 H, H arom., AA´BB´ system, N = 3JAВ + 5JAВ´ = 8.1 Hz).
The solid colorless residue of the fraction with Rf 0.68 (ac-
etone—toluene, 1 : 9) contained 4-chloro-5-[(4-methylphenyl)-
sulfanyl]-2(5H)-furanone (13). Yield 12%, colorless needle
1
crystals, m.p. 46—47 C. H NMR, δ: 2.34 (s, 3 H, CH3); 5.91
4
4
(d, 1 H, C(3)H, JHH = 1.4 Hz); 5.98 (d, 1 H, C(5)H, JHH
=
= 1.4 Hz); 7.14, 7.41 (4 H, H arom., AA´BB´-system, N =
= 3JAВ + 5JAВ´ = 8.0 Hz). 13C NMR, : 21.25 (qt, CH3, 1JCH
= 126.9 Hz, 3JCH = 4.2 Hz); 88.19 (dd, C(5), 1JC(5)H = 169.2 Hz,
3JC(3)H = 7.7 Hz); 119.06 (dd, C(3), 1JC(3)H = 187.9 Hz, 3JC(5)H
= 2.2 Hz); 122.41 (td, Cipso
3JCH 3JC(5)H = 7.3 Hz); 130.02
=
=
,
=
(ddq, Cm, 1JCH = 159.0 Hz, 3JCH = 3JCH(CH3) = 5.2 Hz); 135.94
1
3
(dd, Co, JCH = 163.1 Hz, JCH = 5.8 Hz); 140.63 (qt, Cp,
2JCH(CH )
=
3JCH = 6.6 Hz); 157.37 (d, C(4), JCH = 4.4 Hz);
2
168.07 (3br.s, C(2)). MS, m/z (Irel (%)): 240 [М]+ (94), 123
[pTolS]+ (51), 117 [М – pTolS]+ (18), 92 [pTol + H]+ (100).
The solid oily residue of the fraction with Rf 0.66 (acetone—
toluene, 1 : 9) contained 4,5-di[(4-methylphenyl)sulfanyl]-2(5H)-
furanone (14). Yield 33%. 1H NMR, δ: 2.35 (s, 3 H, CH3); 2.37
(s, 3 H, CH3); 5.07 (d, 1 H, C(3)H, 4JHH = 1.2 Hz); 6.05 (d, 1 H,
C(5)H, 4JHH = 1.2 Hz); 7.13—7.55 (m, 8 H, H arom.). 13C NMR,
: 21.27 (qt, CH3, 1JCH = 126.8 Hz, 3JCH = 4.4 Hz); 86.37 (dd,

5-Thio-substituted 2(5H)-furanone derivatives
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
315
1
3
C(5), JC(5)H = 168.7 Hz, JC(3)H = 8.8 Hz); 112.44 (dd, C(3),
The reduction of furanone 9 on a GC electrode afforded
a more complex mixture of products, in which compound 16 did
not predominate.
1JC(3)H = 184.6 Hz, 3JC(5)H = 2.0 Hz); 124.49 (t, C(4)SAr Cipso
,
=
=
=
3JCH = 9.4 Hz); 129.76 (ddq, Cm, JCH = 158.7 Hz, JCH
1
3
= 3JCH(CH ) = 5.2 Hz); 130.84 (ddq, Cm, 1JCH = 160.3 Hz, 3JCH
Quantum chemical calculations. Calculations for the gas-phase
structures of the starting compounds, reduction products, and
presumable intermediates were performed with full geometry
optimization without symmetry constraints by the DFT//
В3LYP/6-31++G(d,p) method using Gaussian 09 program
package.30 The calculations for solutions in acetonitrile were
carried out by self-consistent reaction field and the PCM con-
tinuum model.31
3
= 3JCH(CH ) = 5.1 Hz); 134.29 (dd, Co, 1JCH = 163.7 Hz, 3JCH
3
1
3
= 5.9 Hz); 135.38 (dd, Co, JCH = 163.1 Hz, JCH = 6.1 Hz);
140.04 (qt, C(4)SAr Cp, 2JCH(CH ) = 3JCH = 6.6 Hz); 140.91 (qt,
C(5)SAr Cp2, 2JCH(CH ) = 3JCH = 63.4 Hz); 169.46 (dd, C(4), 2JCH
=
3
3
= 7.5 Hz, JCH = 2.6 Hz); 170.25 (d, C(2), JC(5)H = 3.3 Hz).
13C{1H} NMR, : 21.27 (CH3); 86.37 (C(5)); 112.44 (C(3)); 124.13,
124.49 (Cipso); 129.75, 130.84 (Cm); 134.29, 135.38 (Co); 140.04, 140.91
(Cp); 169.46 (C(4)); 170.25 (C(2)). MS, m/z (Irel (%)): 328 [М]+
(5), 205 [М – pTolS]+ (100), 177 [М – pTolS – CO]+ (12), 149
[М – pTolS – 2 CO]+ (9), 124 [pTolSH]+ (33), 91 [pTol]+ (52).
Experiment B was carried out in a similar way using a lead elec-
trode (S = 18.4 cm2). Experimental conditions: furanone 6 (0.87 g,
3.2 mmol), Et4NBF4 (0.38 g, 1.8 mmol), AcOH (1.43 mL, 25.4 mmol),
I = 70 mA, electrolysis time 3 h (Q = 2.5 F mol–1), V(Et4NOH) =
= 0.8 mL. According to 1H NMR spectroscopy, the residue
contained furanones 13 and 14 in 1 : 0.4 ratio and disulfide 15.
The reduction of 3,4-dichloro-5-ethylsulfanyl-2(5H)-furanone
(9) was conducted similarly to the reduction of compound 6.
Experimental conditions: furanone 9 (0.84 g, 4.0 mmol), Et4NBF4
(0.38 g, 1.8 mmol) AcOH (1.78 mL, 31.6 mmol), lead electrode
(S = 18.4 cm2), I = 70 mA, electrolysis time 3 h 30 min
(Q = 2.3 F mol–1), V(Et4NOH) = 1.4 mL. According to 1H NMR
spectroscopy, the obtained residue contained 4-monochloro
derivative 16, two unidentified products in 5 : 3 : 1 ratio, and
1,2-diethyldisulfane (17), which could not be separated by column
chromatography.
Results and Discussion
Quantum chemical study of the selectivity of electro-
chemical reduction of compounds 6—8 and 10—12. The
results of quantum chemical calculations for a series of
5-thio-substituted 2(5H)-furanone derivatives are generally
in line with the calculation data obtained previously for
5-alkoxy derivatives 1—4.25 The results of calculations for
the radical anions of compounds 6—8 and 10—12 indicate
that the single-electron transfer in the gas phase is
accompanied by a slight elongation of both C—Cl bonds
and a decrease in the dissociation energy (Table 1). The
decrease in the dissociation energy is greater for thioethers
6—8 (2.0—2.3-fold) than for sulfones 10—12 (1.3—1.5-fold).
The free energy values for the regioisomeric radicals
and anions of sulfones 10—12 (Scheme 2) indicates
a higher thermodynamic stability of 3-chloro-substituted
species R´ and An´ compared with that of 4- chloro-sub-
stituted R and An (Table 2). Hence, in these reduction
steps, like in the case of 5-alkoxy derivatives 1—4, re-
gioselectivity can be expected. For thioehers 6—8, the
An´ species are also more stable than An; however, the
Signals of 4-chloro-5-ethoxy-2(5H)-furanone (16) in the
1H NMR spectrum of the reaction mixture, δ: 1.32 (t, 3 H, Х-part
of the AВХ3-system, CH3, JAХ = JВX = 7.5 Hz); 2.54—2.69 (m,
2 H, OCH2); 5.96 (d, 1 H, C(5)H, 4JH(5)H(3) = 1.6 Hz); 6.25 (d,
1 H, C(3)H, 4JH(3)H(5) = 1.6 Hz). MS, m/z (Irel (%)): 178 [М]+
(20), 149 [М – Et]+ (10), 117 [М – SEt]+ (100), 89 [М – SEt –
– CO]+ (11), 61 [EtS]+ (27).
Table 1. DFT//B3LYP/6–31++G(d,p)-calculated characteristics of the C—Cl and C—S bonds in neutral molecules 6—8 and 10—12
and their radical anions in the gas phase (I) and in acetonitrile solution (II)*
Com- Medium
l(C—Y)n/Å
l(C—Y)ar – l(C—Y)n/Å
Еdis(C—Y)n/kJ mol–1
Еdis(C—Y)ar/kJ mol–1
pound
C(3)–Cl C(4)–Cl C(5)–S C(3)–Cl C(4)–Cl C(5)–S C(3)–Cl C(4)–Cl C(5)–S C(3)–Cl C(4)–Cl C(5)–S
6
I
II
I
II
I
II
I
II
I
II
I
II
I
II
1.7095 1.7124
1.8418
0.0181 0.0194 1.0265
0.0161 0.0234 1.0293
0.0171 0.0186 1.0221
0.0116 0.0178 1.0393
0.0166 0.0175 1.0589
0.0115 0.0176 1.0292
0.0420 0.1750 0.0332
350.6
349.3
351.0
349.3
351.1
349.1
351.3
349.0
352.6
348.4
352.7
350.4
353.0
350.8
351.1
349.7
351.7
349.7
351.8
342.3
343.2
342.6
336.0
333.7
336.6
336.3
337.1
335.9
91.0
88.1
91.2
88.1
95.8
91.8
125.4
124.6
44.2
45.3
43.5
45.7
46.5
48.2
153.7
38.4
174.9
38.4
175.7
38.3
112.4
3.0
248.0
119.9
275.6
133.4
266.3
131.7
154.2
38.9
175.6
38.9
176.5
31.4
104.3
3.4
231.4
105.3
259.6
119.2
250.4
116.8
43.3
–27.8
31.9
–27.8
34.9
–24.4
60.9
16.8
39.1
–22.9
38.3
1.7116 1.7084 1.8391
1.7087 1.7120 1.8431
7
1.7111
1.7087 1.7120 1.8432
1.7111 1.7082 1.8394
1.7095 1.7122 1.8274
1.7119 1.7086 1.8221
1.7062 1.7134 1.9108
1.7074 1.7062 1.9060 –0.0011 0.0153 2.4165
1.7054 1.7135 1.9107 0.0097 0.0084 2.1989
1.7068 1.7060 1.9051 –0.0005 0.0153 2.3661
1.7053 1.7136 1.9106 0.0091 0.0124 2.3544
1.7068 1.7062 1.9055 –0.0007 0.0154 2.3206
1.7081 1.8398
8
9
0.0392 0.1412
0.0217
10
11
12
0.0103 0.0127 2.3701
–21.7
30.8
–21.3
* l is the bond length, Edis is the bond dissociation energy; the subscripts n and ar correspond to neutral molecules and radical anions,
respectively.

316
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
Latypova et al.
Scheme 2
Compound
X
Compound
X
6
7
8
9
4-MeC6H4S
4-ClC6H4S
4-BrC6H4S
EtS
10
11
12
4-MeC6H4SO2
4-ClC6H4SO2
4-BrC6H4SO2
thermodynamic stabilities of the R and R´ radicals are
virtually equal.
In the case of sulfur-containing furanones 6—8 and
10—12, the electron affinity of their R and R´ radicals is
higher than the electron affinity of neutral molecules (see
Table 2), which enables the reductive C—Cl bond cleavage
in these furanones by the ECE mechanism (see Scheme 2).
As in the case of 5-alkoxy derivatives 1—4, the EED
mechanism of ECR is also, in principle, possible for fu-
ranones 6—8 and 10—12 (see Scheme 2). The thermody-

5-Thio-substituted 2(5H)-furanone derivatives
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
317
Table 2. DFT//B3LYP/6–31++G(d,p)-calculated characteristics of the relative
stability (ΔΔG298) and electron affinity (EA) of intermediates and regioisomeric
reduction products of furanones 6—8 and 10—12 in the gas phase (I) and in solution
in acetonitrile (II)
Com-
pound
Medium
ΔΔG298/kJ mol–1
EA/kJ mol–1
R – R´
An – An´
P – P´
ЕАn
EAR
EAR´
6
I
II
I
II
I
II
I
II
I
II
I
II
I
II
–0.5
–0.651
–0.8
–0.449
–0.8
6.867
8.2
13.5
0.386
15.6
0.449
15.8
–6.263
10.2
4.6
14.2
5.597
14.4
17.3
3.5
19.5
3.2
29.3
2.2
23.1
14.7
29.2
12.0
14.8
10.4
19.3
16.2
159.6
320.0
180.4
327.1
181.2
327.1
117.7
291.9
252.0
409.5
279.5
420.9
269.9
418.8
289.9
485.0
305.9
486.8
306.6
486.5
284.6
483.1
320.8
505.5
337.1
509.1
337.8
508.5
303.4
485.4
321.5
487.2
322.3
480.2
294.7
487.7
335.0
511.1
351.5
513.9
351.5
515.5
7
8
9
0.4
10
11
12
16.5
14.654
16.1
14.139
16.0
14.859
4.798
13.7
7.034
namic preference (see Table 2) of formation of the An´
carbanions over An carbanions (G298(An—An´) =
= 13.5—15.8 kJ mol–1) is comparable with this value
for the regioisomeric radicals (G298(R—R´) =
= 16.0—16.5 kJ mol–1) for sulfones 10—12 and is much
higher for thioethers 6—8.
erably lower for the C(5)—S bond of radical anions than
for the C(4)—Cl bond, and the products formed upon
cleavage of this bond proved to be thermodynamically
more stable (see Tables 1, 2).
Thus, the results of quantum chemical investigation of
the structures of furanones 6—8 and 10—12 and the pos-
sible intermediates formed in their ECR provide evidence
for the predominant formation of C(5)—S bond cleavage
products, whereas the selective formation of 3-chloro
derivatives P´ proved to be unlikely. In the reaction pathway
associated with C(5)—S bond cleavage, irrespective of the
reaction mechanism, the leaving group is the arylthiolate
ion, whose capability for elimination is roughly equal to
that of the chloride ion, but is considerably lower than that
of arylsulfinate ion.32
Quantum chemical calculations revealed some consid-
erable differences of sulfur derivatives 6—8 and 10—12
from furanones 1—4, namely, (1) the electron affinity is
much higher (EA = 40—170 kJ mol–1); (2) the common
trend towards weakening of C(4)—Cl and C(3)—Cl bonds
upon single-electron transfer is much less pronounced;
(3) the C(4)—Cl and C(3)—Cl bond dissociation energies
for the radical anions of thioethers 6—8 are virtually equal;
(4) the C(5)—S bond dissociation energy is considerably
lower (see Table 1) than the C(5)—O bond dissociation
energy in the radical anions. Whereas for radical anions
of 5-alkoxy derivatives 1—4, Edis(C(5)—O) is higher than
Edis(C(4)—Cl) or Edis(C(3)—Cl),25 in the case of sulfur
compounds 6—8 and 10—12, Edis(C(5)—S) is, conversely,
markedly lower than the latter values (see Table 1).
Analysis of the calculation results indicates that the
C(5)—S bond cleavage is preferred over the C(4)—Cl bond
cleavage in both ECE and EED mechanisms (see Table 2).
Hence, elimination of the arylthiolate ion rather than the
chloride ion, as in the case of 5-alkoxy derivatives, may
be predicted for these reduction steps.
Electrochemical experiments. Cyclic voltammetry. The
CV curves for the sulfur derivatives 6—8 and 10—12 mea-
sured in МeCN—Вu4NBF4 (0.1 mol L–1) on a GC elec-
trode have identical morphology similar to that of the CV
curves of mucochloric acid 5, but markedly differing from
those of its 5-alkoxy derivatives 1—4 (Fig. 1). For each of
thioethers 6—8 and sulfones 10—12 and also for furanone 5,
three irreversible reduction peaks of comparable intensity
are observed (see Fig. 1, a—c), whereas in the case of
alkoxy derivatives 1—4, one peak is present (see Fig. 1, e).
The first peak current ipred,1 approximately corresponds to
the transfer of one electron per molecule (Table 3) and
increases in proportion with the compound concentration
in the range of 5•10–4—5•10–3 mol L–1. The first peak
has a diffusion nature, as follows from the linear depen-
In order to evaluate the possible influence of the solvent
on the C(5)—S and C(4)—Cl bond cleavage steps, we
calculated the structures of the starting compounds and
intermediates in acetonitrile solutions by the polarized
continuum method (РCМ model).31 However, in aceto-
nitrile solutions, the dissociation energy was also consid-
dence of the first peak current ipred,1 on 1/2
.
As expected, in view of the higher electron affinity of
the R and R´ radicals in comparison with neutral molecules

318
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
Latypova et al.
I/A
I/A
I/A
a
b
c
25 A
25 A
25 A
+1.0
0
–1.0 –2.0 E/V
+1.0
0
–1.0 –2. E/V
+1.0
0
–1.0 –2.0 E/V
I/A
I/A
I/A
d
e
f
25 A
25 A
25 A
+1.0
0
–1.0 –2.0 E/V
+1.0
0
–1.0 –2.0 E/V
+1.0
0
–1.0 –2.0 E/V
Fig. 1. Cyclic voltammograms of thioether 6 (a), sulfone 10 (b), mucochloric acid 5 (c), thioether 9 (d), furanone 1 (e), and 3-chloro-
5-methoxy-2(5H)-furanone (f). C = 3•10–3 mol L–1, МeCN—Вu4NBF4 (0.1 mol L–1), glassy carbon electrode,  = 200 mV s–1. The
potentials E are given versus Ag/AgNO3 (0.01 mol L –1) in MeCN.
(see Scheme 2 and Table 2), the potential values of the
first reduction peaks of compounds 6—8 and 10—12 are
shifted towards less cathodic values relative to those of
5-alkoxy derivatives 1—4 (in the case of 5-(p-tolyl)thio
derivative 6, which is least prone to reduction, the shift
relative to 5-ethoxy furanone 2 is 200 mV). Note that
sulfones 10—12 are reduced much more easily than respec-
tive sulfides 6—9 (Eр = 170—260 mV). The halogen atoms
(Br, Cl) in the para-position of the benzene ring also fa-
cilitate the reduction; this effect is more pronounced for
sulfides than for sulfones (see Table 3). For mucochloric
acid 5 and all of the derivatives 6—8 and 10—12, the sec-
Table 3. Cyclic voltammetry data on the electrochemical reduction of compounds 5—12a
Substrate
–Ерred/Vb
ipred,1/A
Ep/2 – Ep/mVc
nd
Ерreox/Vb
5
6
7
8
1.50, 1.88, 2.21
1.72, 2.06, 2.33
1.63, 1.98, 2.25
115
110
114
195
192
193
193
175
130
105
100
105
185
195
185
185
1.4
1.3
1.2
1.2
1.0
1.1
1.0
0.9
–0.38, +1.05, +1.23
–0.23e, +0.49, +0.88, +1.23e
–0.13, +0.53, +0.95, +1.33
–0.13, +0.98, +1.33
1.58, 1.95, 2.33
9
1.86, 1.96, 2.22, 2.47
1.46, 1.92, 2.20
1.41, 1.95, 2.38, 2.56
1.41, 1.95, 2.20
–0.36, +0.71, +0.88
10
11
12
+0.25, +0.94, +1.35
+0.35, +0.98, +1.35
+ 0.37, +0.83, +1.00, +1.33
a C = 3•10–3 mol L–1, MeCN—Bu4NBF4 (0.1 mol L–1), glassy carbon electrode,  = 100 mV s–1
.
b The potentials are given versus Ag/AgNO3 (0.01 mol L–1) in MeCN.
c The Ep/2 and Ep values were corrected to the potential drop iR using the corresponding values for the revers-
ible reduction of benzophenone.
d The number of electrons transferred at the first reduction potentials per molecule.
e Potentials of p-thiocresol oxidation peaks in the absence and in the presence of 1 equiv. Bu4NOH are +1.14
and –0.25 v, respectively.

5-Thio-substituted 2(5H)-furanone derivatives
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
319
ond and third reduction peaks occur at approximately the
same potentials (see Table 3). This means that the reduc-
tion of these compounds at the first peak potentials affords
the same species, which are further reduced at higher
potentials. This is possible only in the case of reductive
elimination of the substituting group from position 5 of
the lactone ring. The usual leaving groups in the reduction
are anions (anionoid elimination); apparently, in this case,
the leaving groups are also anions, namely, hydroxide,
thiolate, and sulfinate ions. In the case of sulfone 11, one
more, fourth, irreversible reduction peak is observed at
more negative potentials (see Table 3), which is caused by
the two-electron reductive cleavage of the C—Cl bond of
the aromatic moiety.33 A similar reduction of the C—Br
bond in bromobenzenes occurs more easily; probably, this
is why in the case of sulfone 12, this step is reflected in the
CV curve as a separate additional intense peak between
the second and third peaks (see Table 3).
The anionоid elimination of substituents from position
5 of the lactone ring directly follows from analysis of the
reverse branches of CV curves. In the case of potential
reversal at the first reduction peak, the CV curves of all
compounds exhibit intense reoxidation peaks in the po-
tential ranges of –0.43 to –0.50 V for thioethers 6—8 and
–0.2 to +0.06 V for sulfones 10—12. For compound 6,
the potential of this peak strictly corresponds to the oxid-
ation potential of the p-tolylthiolate ion. Although no
correlation of this type was made for reoxidation peaks of
sulfones 10—12 with the corresponding sulfinic acids, the
assignment of the observed reoxidation peaks to the sul-
finate ions is beyond doubt, because arylsulfonyl is a good
leaving group.32 In addition, the sulfinate ion is expected
to be less readily oxidized than the thiolate ion, which is
actually observed in sulfide and sulfone reoxidation ex-
periments. It is noteworthy that other reoxidation peaks
are also present in the CV curves of all mentioned com-
pounds, the intensity of these peaks increasing when the
potential is reversed at the second or third reduction peak
(see Table 3). In this case, it was impossible to find out
whether these steps refer to the oxidation of chloride ions
or some other species generated during reduction. The
potentials of these peaks are similar, but do not correspond
to the oxidation peak of chloride ions; for an Et4NCl solu-
tion of the same concentration, this peak occurs at
Eрох(Cl–) = +0.80–+0.90 V vs. Ag/AgNO3 (0.01 mol L–1),
depending on the state of the electrode surface.
increase in the height of the first peak, which reaches the
two-electron level. The subsequent reduction peaks and
the reoxidation peak of the thiolate ion are retained (Fig. 2).
At more negative potentials in the cathodic region, an
additional reduction peak appears, which can be assigned
red
to the reduction of AcOH (for AcOH, Eр = –2.54 V).
The parameters of the first three reduction peaks are re-
tained as the AcOH concentration in solution increases
by a factor of up to eight. After two- or sixfold increase in
the AcOH concentration, depending on the nature of the
thioether, the reverse branch of the CV curve no longer
exhibits the reoxidation peak for arylthiolate ions (–0.23
to –0.13 V), while the reoxidation peak of thiophenols
occurs at +1.05 to +1.26 V.
As shown previously,25 in the case of 5-alkoxy deriva-
tives 1—4, a reduction peak for the 3-monochloro deriva-
tive appears in the CV curves upon the addition of AcOH;
this peak is shifted towards negative potentials relative to
the peak of the starting furanone by 150—200 mV. The
same trend could be expected of sulfur derivatives 6—8
and 10—12, in particular, the reduction of monochloro
derivatives will be more difficult than that of furanone
3,4-dichloro derivatives, approximately to the same extent.
In the case of thioethers 6—8, no peaks for monochloro
derivatives are present in the predicted range of reduction
potentials at any amount of AcOH (see Fig. 2). The reverse
CV branch does not show the chloride oxidation peak
either. It is evident that even in the presence of excess
AcOH, the desired elimination of the chloride ion from
position 4 does not proceed to any noticeable extent.
Thus, at any amount of AcOH used, (1) elimination
of the sulfinate ion takes place at the first reduction po-
tential of sulfones 10—12; as the acid concentration in-
creases, the reoxidation peak is retained and shifts towards
the positive potentials (Fig. 3), (2) no reduction peaks for
the corresponding monochloro derivatives are present,
and (3) the second and third reduction peaks are retained,
the height of the second peak increases with increasing
acid concentration.
It is of interest that the effect of AcOH on the first step
of reduction of sulfones 10—12 differs from its effect on
the reduction of thioethers 6—8. In the case of sulfones
10—12, the addition of an equimolar amount of AcOH
gives rise to additional peak 1´ just after the first peak at
the same potential for all three sulfones. In the case of
sulfone 10, which is reduced less readily, peak 1´ is super-
imposed onto the first reduction peak, which is manifested
as the first peak broadening and shift towards negative
potentials (see Fig. 3). In the case of sulfones 11 and 12,
peak 1´ occurs as a separate peak with Eрred,1´ = –1.55 V,
which is also partly superimposed onto the first reduction
peak (Fig. 4). Therefore, it is impossible to determine
the partial peak heights and the total height or the num-
ber of electrons in each step and the total number of
electrons.
Since the reduction of both thioethers and sulfones at
potentials of the first peak is accompanied by elimination
of substituent from position 5 of the ring to give the same
heterocyclic moiety, we suggested that the addition of
AcOH would have similar effect on both series of com-
pounds. The addition of acetic acid has different effects
on the shapes of CV curves of thioethers 6—8 and sul-
fones 10—12. In the case of thioethers 6—8, the addi-
tion of an equimolar amount of AcOH causes a twofold

320
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
Latypova et al.
I/A
I/A
I/A
a
b
c
50 A
50 A
50 A
+1.0
0
–1.0 –2.0 E/V
+1.0
0
–1.0 –2.0 E/V
+1.0
0
–1.0 –2.0 E/V
I/A
I/A
d
e
50 A
50 A
+1.0
0
–1.0 –2.0 E/V
+1.0
0
–1.0 –2.0 E/V
Fig. 2. Cyclic voltammograms of thioether 6 (C = 3•10–3 mol L–1) in the absence (а) and in the presence of AcOH in concentrations
of 3•10–3 (b), 6•10–3 (c), 12•10–3 (d), 24•10–3 mol L–1 (e). МeCN—Bu4NBF4 (0.1 mol L–1), glassy carbon electrode,  = 200 mV S–1
.
The potentials E are given versus Ag/AgNO3 (0.01 mol L–1) in MeCN.
When the acid content increases up to eightfold, the
additional peak of all compounds 10—12 coalesces with
the first peak. This is indicated by some first peak broad-
ening and shift towards negative potentials with respect to
the first peak without the acid. At a large excess of AcOH,
the first peak height reaches and exceeds the two-electron
level. It is noteworthy that an additional reduction peak
appears at the same potential in the reduction of the par-
ent mucochloric acid 5 in the presence of stronger formic
acid. It is evident that the reduction of furanone 5 gives
a product analogous to the reduction products of sulfones.
Apparently, a similar additional peak 1´ is also present
in the CV curves of thioethers 6—8, but it is hidden under
the first reduction peak, because thioethers are reduced
less readily than sulfones. The twofold increase in the
current of the first reduction peak of thioethers after the
addition of an equimolar amount of AcOH is caused not
only by the increase in the first peak height, but also by
appearance of new peak 1´.
by the ECE or EED mechanism as the transfer of two
electrons with C(5)—S bond cleavage to give arylthiolate
(arylsulfinate) ions and heterocyclic carbanion (Schemes 2
and 3). The observed reoxidation peak refers to the oxid-
ation of the corresponding arylthiolate and arylsulfinate
anions. In the presence of AcOH, the arylthiolate ion is
protonated; therefore, the peak for its reoxidation dis-
appears. Arylsulfinic acid is stronger than acetic acid
(рКа(p-MeC6H4SO2H) = 1.7, рКа(AcOH) = 4.7634);
therefore, the arylsulfinate ion is not protonated with
AcOH and peak of its oxidation is still detected in the
presence of the acid. The proposed scheme is also sup-
ported by equal potentials of the second and third reduc-
tion peaks corresponding to the reduction products that
are formed upon elimination of the substituent from posi-
tion 5 of the heterocyclic moiety.
This brings about the question of the subsequent trans-
formations of the primarily generated heterocyclic Fur–
carbanion (see Scheme 3), i.e., what products are formed
and reduced at the potentials of additional peak 1´ and
subsequent peaks? Since the Fur– carbanion is not reduced
The whole set of obtained results indicates that the
reduction of thioethers 6—8 and sulfones 10—12 occurs

5-Thio-substituted 2(5H)-furanone derivatives
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
321
I/A
I/A
I/A
a
b
c
50 A
50 A
50 A
+2.0 +1.0
0
–1.0 –2.0 E/V
+2.0 +1.0
0
–1.0 –2.0 E/V
I/A
+2.0 +1.0
0
–1.0 –2.0 E/V
I/A
d
e
100 A
100 A
+2.0 +1.0
0
–1.0 –2.0 E/V
+2.0 +1.0
0 –1.0 –2.0 E/V
Fig. 3. Cyclic voltammograms of sulfone 10 (C = 3•10–3 mol L–1) in the absence (а) and in the presence of AcOH in concentrations
of 3•10–3 (b), 6•10–3 (c), 12•10–3 (d), 18•10–3 mol L–1 (e). МeCN—Bu4NBF4 (0.1 mol L–1), glassy carbon electrode,  = 200 mV s–1
The potentials E are given versus Ag/AgNO3 (0.01 mol L–1) in MeCN.
.
I/A
I/A
50 A
I/A
50 A
a
b
c
50 A
+2.0 +1.0 0 –1.0 –2.0 E/V
+2.0 +1.0
I/A
0
–1.0 –2.0
E/V
+2.0 +1.0
0
–1.0 –2.0
E/V
I/A
I/A
d
e
f
50 A
50 A
50 A
+2.0 +1.0
0
–1.0 –2.0
E/V
+2.0+1.0
0 –1.0 –2.0 E/V
+2.0+1.0 0 –1.0 –2.0 E/V
Fig. 4. Cyclic voltammograms of sulfone 12 (C = 3•10–3 mol L–1) in the absence (а) and in the presence of AcOH in concentrations
of 3•10–3 (b), 6•10–3 (c), 12•10–3 (d), 18•10–3 (e), 24•10–3 mol L–1 (f). МeCN—Bu4NBF4 (0.1 mol L–1), glassy carbon electrode,
 = 200 mV S–1. The potentials E are given versus Ag/AgNO3 (0.01 mol L–1) in MeCN.

322
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
Latypova et al.
Scheme 3
in the considered range of potentials (in the absence of
a proton donor, the height of the first peak corresponds
to the transfer of less than two electrons), then, apparently,
under these conditions, this carbanion partly reacts with
the initial molecule to give compounds that are not reduced
at the first-peak potentials and that are apparently poly-
meric (oligomeric) products (resins). The Fur– carbanion
is a rather strong base and it is the first to be protonated
with AcOH. Therefore, when AcOH is added in an equi-
molar amount, it is entirely spent for the protonation of
the carbanion, while arylthiolate is retained as an ion.
Presumably, even in the absence of AcOH, the Fur– carb-
anion is not involved quantitatively in the reaction with
the starting compound, but is partly protonated by the
residual amount of water present in the solution. The
resulting protonation products are probably reduced at the
potentials of subsequent peaks.
The Fur– carbanion can be represented as three reso-
nance structures whose protonation would give rise to
three cyclic tautomers A, В, and C and acyclic isomer D
(see Scheme 3); the most stable of them are dialdehyde D
and 3,4-dichlorofuranone A. The protonation rate and,
hence, the ratio of products A—D can be different depend-
ing on the nature of the proton donor. For the protonation
with water molecules, it cannot be ruled out that the for-
mation of products A—D is thermodynamically controlled,
because this generates the hydroxide ion, a strong base,
which is able to eliminate protons from the products
formed. However, when AcOH is used as the proton donor,
this reaction pathway is relatively unlikely, because the
acetate ion is a weak base. Out of the presented structures
A—D, the conjugated dialdehyde D should be reduced
most easily. The additional peak 1´ may be attributable to
its reduction. The introduction of AcOH accelerates the

5-Thio-substituted 2(5H)-furanone derivatives
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
323
protonation of the Fur– carbanion and, hence, increases
the yield of the protonation products (therefore, the height
of the second peak corresponding to the reduction of these
compounds increases) and decreases the contribution of
the parallel reaction of the carbanion with the starting
compound. Consequently, the height of the first reduction
peak also increases and, in the limiting case, when a large
excess of AcOH is present and this reaction is completely
eliminated, this height should reach the two-electron level.
In view of the fact that additional peak 1´ is superimposed
on the first peak, the height of the overall peak should
exceed the two-electron level, which is actually observed
in experiments.
Scheme 4
Thus, the CV data agree with quantum chemical cal-
culations and attest to elimination of the substituent from
position 5 of the ring and low probability of selective
elimination of chloride ions during the ECR of thioethers
6—8 and sulfones 10—12 in acetonitrile with Bu4NBF4 as
the supporting electrolyte (C = 0.1 mol L–1).
In solution, ions are solvated and form ion pairs. The
supporting electrolyte cation (Bu4N+) also forms ion pairs
with the chloride, arylthiolate, and arylsulfinate ions. Since
the solvation energy and the ion pair interaction energy
depend on the size of ions, we assumed that the probabil-
ity of chloride ion elimination would increase with increas-
ing polarity of the solvent and decreasing radius of the
cation of the supporting electrolyte. Therefore, we carried
out CV experiments in MeCN in the presence of Et4NBF4,
NaClO4, and LiClO4 (C = 0.1 mol L–1) and in mixed
H2O—MeCN and H2O—EtOH solutions (1 : 1) in the
presence of Et4NBF4 for 5-(p-tolyl) thioether 6, in which
elimination of p-tolylthiolate ion is most difficult and
elimination of the chloride ion is most probable. However,
in all cases, CV curves exhibit an intense reoxidation peak
for p-tolylthiolate. Hence, in the reduction in the presence
of any of the supporting electrolytes, elimination of the
p-tolylthiolate ion is the predominant process in all media.
In addition, with NaClO4 and LiClO4, complete passiv-
ation of the electrode surface is observed after the furanone
6 reduction peak is attained.
Preparative electrolysis. In order to prove elimination
of the substituent from heterocycle position 5 at the pre-
parative level and identify the products of reduction of thio
derivatives, we carried out a series of preparative elec-
trolyses in the presence of AcOH. The preparative reduc-
tion of thioether 6 was carried out in the presence of
a fourfold excess of the acid, the reaction being monitored
by CV. The exhaustive reduction (Q = 2.8 F mol–1) on
a GC cathode gave a mixture of products, which were
separated by column chromatography, with disulfide 15,
4-chloro-5-(p-tolylthio)-2(5H)-furanone (13), and 4,5-di-
(p-tolylthio)-2(5H)-furanone (14) being isolated (Scheme 4).
The structure of reduction products was proved by 1H and
13C NMR spectroscopy, 2D NMR spectroscopy, and gas
chromatography–mass spectrometry.
i. Electrochemical reduction, GC electrode, MeCN, Et4NBF4,
AcOH.
The reduction of the C—Cl bond in position 3 of the
ring was evaluated from the 2D 1H—13C HMQC data,
which made it possible to correlate the observed signal of
the vinyl proton with the C(3) carbon signal. In the HMQC
spectrum of compound 13, the cross-peak at δ 5.98/88.19
corresponds to the coupled C(5)—H atoms, while the
cross-peak at δ 5.91/119.06 is due to the correlation of
coupled C(3)—H atoms.
Disulfide 15 is the product of oxidation of thiolate ion,
while furanone 14 results from the nucleophilic attack by
the thiolate ion on the C(4) carbon atom of the lactone
ring of molecule 13 or 6 followed by reduction. The forma-
tion of these compounds at the preparative level confirms,
to some extent, the data on the reductive elimination of
the thiolate ion obtained by cyclic voltammetry and quan-
tum chemical calculations. However, the formation of
4-monochlorinated furanone 13 upon the reductive elim-
ination of the chloride ion from position 3 of the hetero-
cycle was unexpected. After the preparative reduction of
1
thioether 6 on a lead electrode, H NMR spectroscopy
revealed furanones 13 and 14 in 1 : 0.4 ratio and disulfide
15 to be present in the reaction mixture. In the case of
using glassy carbon, the ratio of products 13 and 14 in the
reaction mixture was 0.8 : 1. Apparently, lead electrode
promotes the formation of compound 13. The reduction
both under cyclic voltammetry and under preparative
electrolysis conditions on a GC electrode is characterized
by slightly predominating elimination of the thiolate ion
from position 5 of the heterocycle, while in the case of
lead electrode, this process is accompanied by competing
elimination of the chloride ion from position 3. The results
of preparative macroelectrolysis are in line with CV data

324
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
Latypova et al.
on elimination of the thiolate ion; however, the informa-
tion on the major products of transformation of the hete-
rocyclic moiety could not be obtained by preparative
electrolysis.
Since according to CV data, the reduction of muco-
chloric acid 5 gives the same heterocyclic product as the
reduction of thioethers 6—8 and sulfones 10—12, we car-
ried out additional macroelectrolysis by reducing com-
pound 5 in the presence of a 1.5-fold excess of formic acid
at low current densities (Q = 1.5 F mol–1). These condi-
tions were chosen deliberately to maximize the yield of the
product reduced at potentials of additional peak 1´.
However, as previously,25 no single products were isolated
from the reaction mixture.
Thus, the results of preparative electrolysis also attest
to the predominant elimination of the thiolate ion during
the ECR of thioether 6, whereas in the reduction of
5-alkoxy-3,4-dichloro-2(5H)-furanones 1—4, elimination
of the chloride ion from position 4 of the lactone ring takes
place quantitatively and selectively. 25
This raises the question of what factor is responsible
for the change in the reduction mechanism on going from
5-alkoxy- to 5-arylthio derivatives. In the case of 5-arylthio
derivatives, the solvation energies of the anions attest in
favor of chloride ion elimination, as its solvation energy
in acetonitrile is higher than the solvation energy of the
arylthiolate ion. However, lower C(5)—S bond energy than
the C(5)—O bond energy and higher stability of the aryl-
thiolate ion than the alkoxide ion stability are the reasons
pointing to arylthiolate elimination. In view of the calcu-
lation and experimental results, these structural factors
are likely to prevail over the solvation factor.
We assumed that the C—S bond energy can be in-
creased and the leaving group stability can be decreased
by replacing the arylthio by an alkylthio group; however,
the solvation energy will also increase. Similarly, it is pos-
sible to decrease the C—O bond energy and increase the
stability of the leaving anion, with simultaneous loss of
solvation energy, by replacement of alkyl group in the
molecules of 5-alkoxy derivatives by an aryl group. There-
fore, presumably, 5-aryloxy and 5-alkylthio mucochloric
acid derivatives would occupy an intermediate position
between 5-alkoxy and 5-arylthio derivatives in the ability
to eliminate the chloride ion from position 4 and sub-
stituent from position 5. In the case of 5-alkoxy and
5-arylthio derivatives, it is more likely that the two elimi-
nation processes occur in parallel, which is consistent with
quantum chemical data. As the arylthio group is replaced
by an ethylthio group, the C(5)—S bond rupture energy
markedly increases both in the starting compound 9 and
in the radical anion. In the gas phase, elimination of the
ethylthiolate ion is energetically favorable, while in ace-
tonitrile, the favorable process is chloride ion elimination
from position 3 or 4 (see Table 2).
In order to verify these assumptions, we synthesized
5-ethylthio furanone derivative 9 and investigated its
electrochemical properties (Fig. 5). The CV curves of
thioether 9 measured on various electrodes (Table 4) show
one intense irreversible two-electron reduction peak at
a potential close to the reduction potential of the corre-
sponding 5-ethoxy derivative 2.25 In addition, several more
peaks with lower intensity are present.
The morphology of the CV curves of thioether 9 is
similar to that of 5-alkoxy derivatives 1—4, although dif-
I/A
I/A
I/A
a
b
c
25 A
25A
25 A
–1.2 –1.6 –2.0 –2.4
E/V
–1.2 –1.6 –2.0 –2.4
E/V
–1.2 –1.6 –2.0 –2.4
E/V
I/A
I/A
d
e
25 A
25 A
–1.2 –1.6 –2.0 –2.4
E/V
–1.2 –1.6 –2.0 –2.4
E/V
Fig. 5. Cyclic voltammograms of thioether 9 (C = 3•10–3 mol L–1) in the absence (а) and in the presence of AcOH in concentrations
of 3•10–3 (b), 6•10–3 (c), 12•10–3 (d), 24•10–3 mol L–1 (e). МeCN—Bu4NBF4 (0.1 mol L–1), glassy carbon electrode,  = 100 mV s–1
The potentials E are given versus Ag/AgNO3 (0.01 mol L–1) in MeCN.
.

5-Thio-substituted 2(5H)-furanone derivatives
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
325
Table 4. Reduction potentials of compound
9 on various electrodesa,b
Scheme 5
Electrode
–Ерred/V
GC
Pb
Ag
Pt
Cu
Hg
1.86, 1.99, 2.26
1.81
1.85, 1.99
1.92
1.81
1.84
Unidentified products
a
Potentials are given versus Ag/AgNO3
(0.01 mol L–1).
ECR is electrochemical reduction.
b C = 3•10–3 mol L–1, MeCN—Bu4NBF4
(0.1 mol L–1),  = 100 mV s–1
.
compound 16 can be presumably identified as 4-chloro-
5-ethoxy-2(5H)-furanone. This is indicated by the pres-
ence of a triplet and a multiplet typical of ethoxy group
protons and two doublets at  5.96 and 6.25 (3JHH = 1.6 Hz)
corresponding to the methine proton at the C(5) car-
bon atom and the vinylic proton at C(3). In our opin-
ion, the signal at  6.25 corresponds to the vinylic pro-
ton at C(3) rather than at C(4), because the C(4)H
proton is more deshielded and is expected to resonate at
 ≈ 7.0, which is actually observed for 3-monochloro
derivatives.25
Thus, the results of preparative microelectrolysis are
more or less consistent with the assumed competitive
elimination of the chloride ion and ethylthiolate ion in the
ECR of compound 9 at the first peak potentials.
General views on the mechanism of reduction of 2(5H)-
furanone derivatives. Application of a set of methods
(quantum chemical calculations, cyclic voltammetry, and
preparative microelectrolysis) gives a comprehensive view
on the electrochemical behavior of 2(5H)-furanone de-
rivatives at first peak potentials in acetonitrile.
The reduction of 5-alkoxy derivatives 1—4 on a lead
and GC electrodes in the presence of AcOH as proton
donor is a highly selective reaction giving 5-alkoxy-3-
chloro-2(5H)-furanones.25 The performed analysis of
experimental data and quantum chemical calculations
for the structures of possible intermediates led to the
conclusion that the EEDC mechanism comprising a tan-
dem transfer of two electrons with chloride ion elimina-
tion in the step of second electron transfer and pro-
tonation is the most likely ECR mechanism for com-
pounds 1—4.25
In the ECR of mucochloric acid 5 and 5-arylsulfanyl-
and 5-arylsulfonyl-3,4-dichloro-2(5H)-furanones, an-
ionoid elimination of the substituent from position 5 of
the lactone ring is the predominant process. The contribu-
tion of the competing elimination of the chloride ion in-
creases on going to 3,4-dichloro-5-ethylsulfanyl-2(5H)-
furanone (9).
fers somewhat by the presence of additional peaks (cf.
Fig. 1, e and Fig. 5, a). This may indicate that reduction
of compound 9 is accompanied by competitive elimination
of the chloride ion and ethylthiolate ion, with the former
process predominating. These preliminary conclusions are
in line with virtually all of the obtained results. The reverse
branch of the CV curve shows reoxidation peaks for both
the ethylthiolate ion (Eрreox,1 = –0.36 V) and chloride ion
(Eрreox,2 = +0.88 V). The addition of AcOH to the solution
increases the height of both the first reduction peak and
red,2
the second low-intensity peak Eр
= –1.96 V (see
Fig. 5), which can be assigned, by analogy with 5-alkoxy
derivatives, to the reduction of monochloro 2(5H)-fur-
anone derivative. The height of this peak increases with
increasing concentration of the acid, but does not reach
the level of the corresponding peak of 5-alkoxy deriva-
tives even with large excess of AcOH (see Fig. 5). This
means that elimination of the chloride ion is not quan-
titative in this case, but competes with elimination of
the ethylthiolate ion. The CV curves measured in the pres-
ence of AcOH exhibit many other peaks of different in-
tensity, which also points to formation of several products
(see Fig. 5).
Further, we carried out the preparative reduction of
compound 9 in the presence of an eightfold excess of
AcOH both on a lead electrode and on a GC electrode;
in both cases, a complex mixture of products was obtained
1
(Scheme 5). Using GC/MS and H NMR spectroscopy,
the major products were identified in the reaction mixture,
namely, monochloro derivative 16, diethyl disulfide 17,
and some other unidentified furanone derivatives, which
could not be isolated in a pure state. This result supports
the competition between elimination of chloride and ethyl-
thiolate ions during the reduction of compound 9 at the
first peak potentials.
According to the 1H NMR data for the reaction mixture
and some isolated fractions resulting from attempted
separation of the mixtures by column chromatography,

326
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
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pose a simple experimental criterion for one or another
pathway of electrochemical reduction using only CV data
without resorting to the whole set of studies. For 3,4-di-
chloro-2(5H)-furanone derivatives reduced with selective
elimination of 4-substituent, the CV curves measured in
a MeCN—Bu4NBF4 (0.1 mol L–1) solution exhibit one
intense reduction peak, while for derivatives that are re-
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of comparable intensity are present. Therefore, there is
no need to record the complete CV curve; it is sufficient
to measure only the forward branch and determine
the number of reduction peaks. If the forward branch
exhibits one intense peak, elimination of the chloride ion
takes place; if three peaks are present, elimination of the
5-substituent occurs. The presence of some other peaks
of a different morphology attests to a different ECR
mechanism.
The authors are grateful to the staff of the Collective
Spectral-Analytical Center of FRC Kazan Scientific Center
of Russian Academy of Sciences for gas chromatography–
mass spectrometry analysis.
This work was financially supported by the Ministry of
Education and Science of the Russian Federation accord-
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Received December 1, 2018;
in revised form December 28, 2018;
accepted January 21, 2019