Alkene, Bromide, and ROH – How To Achieve Selectivity? Electrochemical Synthesis of Bromohydrins and Their Ethers

Article abstract of DOI:10.1002/adsc.202100161

Bromohydrins and their ethers were electrochemically synthesized via hydroxy- and alkoxybromination of alkenes using potassium bromide and water or alcohols. High selectivity of bromohydrins formation was achieved only with the use of DMSO as the solvent and an acid as the additive. The proposed combination of starting reagents, additives, and solvents allowed to form bromohydrins or their ethers selectively despite the variety of side-products (epoxides, dibromides, diols). Bromohydrins were obtained in high yields, up to 96%, with a broad substrate scope in an undivided electrochemical cell equipped with glassy carbon and platinum electrodes at high current density. (Figure presented.).

Full text of DOI:10.1002/adsc.202100161

RESEARCH ARTICLE
DOI: 10.1002/adsc.202100161
Alkene, Bromide, and ROH – How To Achieve Selectivity?
Electrochemical Synthesis of Bromohydrins and Their Ethers
Oleg V. Bityukov,a, b Vera A. Vil’,a, b Gennady I. Nikishin,a and
Alexander O. Terent’eva, b,*
a
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp.,
119991 Moscow, Russian Federation
All-Russian Research Institute for Phytopathology, B. Vyazyomy, Moscow Region, 143050, Russian Federation
b
Phone: (+7)-91638540
E-mail: terentev@ioc.ac.ru
Manuscript received: February 3, 2021; Revised manuscript received: April 1, 2021;
Version of record online: ■■■, ■■■■
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.202100161
Abstract: Bromohydrins and their ethers were electrochemically synthesized via hydroxy- and alkoxybromi-
nation of alkenes using potassium bromide and water or alcohols. High selectivity of bromohydrins formation
was achieved only with the use of DMSO as the solvent and an acid as the additive. The proposed combination
of starting reagents, additives, and solvents allowed to form bromohydrins or their ethers selectively despite
the variety of side-products (epoxides, dibromides, diols). Bromohydrins were obtained in high yields, up to
96%, with a broad substrate scope in an undivided electrochemical cell equipped with glassy carbon and
platinum electrodes at high current density.
Keywords: Alkene difunctionalization; Potassium bromide; Electrosynthesis; Bromohydrins; CÀ O bond
Introduction
In the electroorganic experiment, electric current
can serve both as an oxidant and as a reductant, the
The importance of halohydrins in organic chemistry[1] “reactivity” of which can be finely tuned by the nature
is illustrated by their utility in the synthesis of of electrodes, electrolyte, solvent, cell type, and
epoxides,[2] ketones,[3] α-alkenyl ketones,[4] amino electrolysis mode (potentiostatic or galvanostatic).[21]
acids,[5] cyclic carbonates,[6] 2-oxazolidinones,[7] and O- Solving the problem of selective synthesis under
alkylated oximes[8] as well as in cross-coupling variability of the experimental options and many
processes.[9] Potentially, the simplest approach to possible side processes determines the high level of
bromohydrins starts from alkenes and requires stoi- scientific novelty in the development of selective
chiometric amount of N-bromoimides,[10] [bmim]BF4- electroorganic reactions.[21a,22]
water/NBS,[11] KBr/I2O5,[12] HBr/DMSO,[13] tribromoi-
Alkenes offer an excellent starting point for the
socyanuric acid,[14] chloramine-T trihydrate,[15] N,N- electrochemical organic synthesis due to their
dibromo-p-toluenesulfonamide,[16] HBr/H2O2,[17] and abundance.[23] Electrochemical oxidative difunctionali-
Br2 (or Br2/BrÀ )/H2O.[18] The two-step protocols from zation of alkenes has proven to be one of the most
alkenes to halohydrins via the reaction of the promising approaches to increasing molecular
intermediate epoxides with halides[19] are also known. complexity.[24] A lot of transformations of alkenes in
However, most of these processes are associated with alcohol media proceed in an electrochemical cell: α,β-
the formation of side products such as vicinal dihalides dialkoxylation,[25] α-alkoxy-β-hydroxylation,[26] α,α-
and diols,[15,20] require several synthetic steps and dialkoxylation,[27] allylic oxidation,[25b] dimerization
produce huge amount of waste. One of the main ideas with various regioselectivity,[25d,28] and oxidative cleav-
of our work lies in the replacement of stoichiometric age of C=C bonds.[26,29]
chemical reagents by an electric current, mostly with
The addition of bromide salts into the alkene/ROH
the involvement of anodic processes, for the trans- system increases the variability of the electrochemical
formation of alkenes into halohydrins.
transformation of alkenes. Alkene electrolysis in the
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presence of BrÀ /ROH leads to the mixture of bromohy- difunctionalization. Herein, we describe the synthetic
drins ethers with different regioselectivity, α,β-dibro- approach to bromohydrins and their ethers via electro-
mides, and α,β-dialkoxylated products[30] or α,α-dia- chemical alkene hydroxy- or alkoxybromination. The
lkoxy-β-bromide[31] under CCE (constant current selectivity is achieved by applying DMSO or CH3CN
electrolysis) mode, and to the mixture of α,β-dibro- as the solvent and an acid as the additive.
mides, α,β-dialkoxylated products, and bromohydrins
ethers under CPE (controlled potential electrolysis)
Results and Discussion
mode[32] (Scheme 1, a). Also, bromohydrins in an
electrochemical cell undergo cyclization to form As the first step, we explored the electrolysis of styrene
epoxides.[33]
1a using potassium bromide as the supporting electro-
The earlier discussed studies[25–33] could make one lyte in water (Scheme 2). At the first glance, it seems
think that investigation of the “alkene, bromide, ROH, that the system alkene / bromine-containing electrolyte
electric current” system is hopeless from the novelty / H2O is sufficient for electrochemical synthesis of
point of view and that the chances of creating a bromohydrins. However, this reaction led to a mixture
selective process are slim. The problem of low of the following products: 2-bromo-1-phenylethanol
selectivity in the synthesis of bromohydrins or their 2a, styrene oxide 3, (1,2-dibromoethyl)benzene 4, 1-
ethers[30–32] is determined by the fact that using only the phenylethane-1,2-diol 5 (Scheme 2). Conversion of the
obvious reaction components, which form the target starting styrene 1a and the composition of the mixture
products, does not allow to achieve high selectivity. did not change when electric current amount passed
The idea of the present study is to change the reactivity per 1 mole 1a increased from 4 F/mol to 8 F/mol
of the starting system using “switching” components. (Scheme 2).
Keeping in mind the potential of electroorganic
Surprisingly, the addition of acetic acid as the first
chemistry, we discovered that the appropriate co- “switching” component into the reaction mixture
solvent and the acid greatly change the transformation resulted in increased yield of bromohydrin 2a (42%)
way of “alkene, bromide, ROH, electric current” and decreased yield of (1,2-dibromoethyl)benzene 4
system. In our study, bromohydrins and their ethers (6%) (Table 1, entry 1). In this case, we did not
were selectively obtained despite the numerous possi- observe the formation of styrene oxide 3 and 1-
ble transformations of alkenes in an undivided electro- phenylethane-1,2-diol 5.
chemical cell in the presence of alcohols and halides
(Scheme 1, b).
This result inspired us to explore another “switch-
ing” additive, the solvent,[35] to increase the yield of 2-
It is known that halogen cations stabilized by bromo-1-phenylethan-1-ol 2a (Table 1).
DMSO (Hal+/DMSO) can be generated by electro-
It was found that using the 1:1 DMSO:H2O system
chemical oxidation of corresponding anions (HalÀ ).[34] led to a 85% yield of bromohydrin 2a (Table 1,
These pre-synthesized halogen cation pools were used entry 5). H2O, THF:H2O, CH3OH:H2O and CH3CN:
for the synthesis of α-haloketones and halohydrins H2O solvent systems were less effective (entries 1–4).
from alkenes.[34] However, there are no known methods The DMSO:H2O ratio had a great influence on 2a
for electrochemical difunctionalization of alkenes with yield (entries 6, 7).
such species, generated directly in the process of
It was shown that the most important parameters,
which determined the selectivity of the electrochemical
reaction, were the use of DMSO as the co-solvent and
the addition of an acid into the reaction mixture. Due
to a great number of experiments, the full details of the
influence of acid nature, electrolyte type, the amount
of electricity passed, solvent system, reaction temper-
Scheme 1. Electrochemical transformations of alkenes in BrÀ /
Scheme 2. Electrochemical transformations of styrene 1a in
ROH system - old guard reagents for modern electrosynthesis.
KBr/H2O system.
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Table 1. The influence of the reaction media on 2a yield.[a]
ethan-1-ol 2a in an undivided electrochemical cell
under constant current electrolysis (Table 2).
In the standard conditions, the yield of 2a was 86%
(entry 1, Table 1). An attempt to carry out the target
process without AcOH was unsuccessful - the bromo-
hydrin 2a was not detected (entry 2). Yield of 2a
decreased to 54% when H2SO4 was used instead of
AcOH (entry 3). However, the use of CF3COOH
increased the yield of 2a to 90% (entry 4). The
reaction did not occur in the absence of electric current
(entry 5). Yield of 2a remained good (75%) under the
constant current of 400 mA (j=106.7 mA/cm2, en-
try 6) and 100 mA (j=26.7 mA/cm2, 86%, entry 7).
Changing the cathode material did not improved the
yield of 2a (entries 8, 9). Increasing the amount of
passed electricity from 4 to 12 F/mol led to a
significantly lower yield of 2a (76%) (entry 10). It was
found that increasing the amount of passed electricity
and the use of TFA afforded the target bromohydrines
2a in a high 91% yield (entry 11).
Entry
Solvent
Yield of 2a, %
1
2
3
4
5
6
7
H2O
42[b]
44
34
76
85
48
49
THF:H2O (1:1)
CH3OH:H2O (1:1)
CH3CN:H2O (1:1)
DMSO:H2O (1:1)
DMSO:H2O (4:1)
DMSO:H2O (1:4)
[a] Reaction conditions: undivided cell, glassy carbon plate
anode (GC) (15 mm×25 mm×2 mm), platinum plate cathode
(15 mm×25 mm×0.4 mm), constant current=200 mA (j=
53.3 mA/cm2), 1a (1 mmol, 104 mg), AcOH (10 mmol,
600 mg), KBr (5 mmol, 595 mg), solvent system (10 mL).
[b] 6% (1,2-dibromoethyl)benzene 4 as by-product.
In order to investigate the scope of the discovered
process and to evaluate the differences in reactivity of
various alkenes 1a–s, the following three slightly
modified methods were used: method A – standard
condition (Table 2, entry 1), method B – conditions of
entry 10, Table 2, method C – conditions of entry 11,
Table 2 (Table 3).
Table 2. The influence of the reaction conditions on 2a yield.[a]
Various substituted aryl alkenes 1a-p possessing
both electron-donating and electron-withdrawing
groups successfully entered the developed process
leading to the target bromohydrins 2a–p in yields from
good to high (Table 3). The exceptions were bromohy-
drins 2m, 2n with N-heterocyclic core, which were
formed in 16–31% yields, probably due to protonation
of the nitrogen atom, resulting in a decrease in the
electron density at the C=C bond. Bromohydrins 2q,
2r from aliphatic alkenes cyclohexene and cyclo-
pentene were synthesized in moderate yields. Allylben-
zene 1s was transformed into a mixture of regioiso-
meric bromohydrins 2s and 2 s’ in a total yield 45%
using method B. In most cases, method C led to better
yields of bromohydrins than methods A and B.
Bromohydrins 2l, 2m, 2o, and 2s (with 2 s’) were
prepared in higher yields through method B.
We also found that the addition of co-solvent and
acid had a great impact on bromohydrin ether 6a
synthesis from styrene 1a (Table 4).
Electrolysis of 1a with KBr as the electrolyte
(5 eq.), in the CH3CN/CH3OH system in the presence
of AcOH (5 eq.) at constant current of 200 mA (the
total of 4 F/mol electric current amount passed per mol
1a) gave 6a in a high 87% yield (entry 1, Table 4).
Entry Deviation from the standard conditions
Yield of
2a, %
1
none
86
n.d.
54
90
n.d.
75
2
without AcOH
3
4
5
H2SO4 instead of AcOH
TFA instead of AcOH
without current
6
7
400 mA instead of 200 mA
100 mA instead of 200 mA
86
8
9
10
11
GC(+) j GC(À ) instead of GC(+) j Pt(À ) 61
GC(+) j Cu(À ) instead of GC(+) j Pt(À ) 65
12 F/mol instead of 4 F/mol
TFA and 12 F/mol instead of AcOH
and 4 F/mol
76
91
[a] Reaction conditions: undivided cell, glassy carbon plate
anode (15 mm×25 mm×2 mm), platinum plate cathode
(15 mm×25 mm×0.4 mm), constant current=200 mA (j=
53.3 mA/cm2), 1a (1 mmol, 104 mg), AcOH (5 mmol,
300 mg), KBr (5 mmol, 595 mg), solvent system (DMSO/
H2O=5 mL/5 mL). n.d.=not determined. TFA=trifluoroa-
cetic acid.
ature on the yield of 2a are presented in SI The experiment without AcOH led to a 21% yield of
(Tables S1–S7). 6a (entry 2). The reaction did not occur without an
Table 2 presents an impact of key parameters on the electric current (entry 3). Surprisingly, yield of 6a in
transformation of styrene 1a into 2-bromo-1-phenyl- neat methanol was lower in comparison with the
CH3CN/CH3OH mixture (entry 4). Replacement of
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Table 3. Electrochemical synthesis of bromohydrins 2a-s from
alkenes 1a-s.
Table 4. The influence of the reaction conditions on bromohy-
drin ether 6a synthesis.[a]
Entry
Deviation from the standard conditions
Yield of
6a, %
1
2
3
4
5
none
without AcOH
without current
CH3OH (10 mL) as the solvent
DMSO/CH3OH (5 mL/5 mL)
as the solvent
87
21
n.d.
82
2a, 86%[a], 76%[b], 2b, 58%[a], 71%[b], 2c, 60%[a], 73%[b],
91%[c]
93% [c]
89%[c]
29
6
7
12 F/mol instead of 4 F/mol
TFA instead of AcOH
89
76
2d, 70%[a], 65%[b], 2e, 56%[a], 73%[b], 2f, 57%[a], 73% [b]
91%[c] 94%[c] 75%[c]
,
[a] Reaction conditions: undivided cell, glassy carbon plate
anode (15 mm×25 mm×2 mm), platinum plate cathode
(15 mm×25 mm×0.4 mm), constant current=200 mA, 1a
(1 mmol, 104 mg), AcOH (5 mmol, 300 mg), KBr (5 mmol,
595 mg), solvent system (CH3CN/CH3OH=5 mL/5 mL). n.
d.=not determined
2g, 46%,[a], 54%[b], 2h, 59%[a], 66%[b], 2i, 61%[a], 58%[b],
87%[c] 96%[c] 92%[c]
CH3CN by DMSO (entry 5, Table 4) provided the
target ether 6a in a low yield. A possible reason is
oxidation of alcohols into ketones in the presence of
dimethyl sulfoxide and bromine,[36] or the formation of
alkoxysulfonium ion intermediates, which are not
hydrolyzed by CH3OH into product 6a.[37] The increase
in the amount of passed electricity to 12 F/mol had a
positive effect on 6a yield (entry 6, Table 4). The use
of TFA instead of AcOH led to lower 76% yield of
bromohydrin ether 6a (entry 7, Table 4).
2j, 48%[a], 43%[b], 2k, 81%[a], 67%[b], 2l, 49%[a], 52%[b],
69%[c] 82%[c] 31%[c]
2m, trace[a], 16%[b], 2n, 33%[a], 31%[b], 2o, 51%[a], 55%[b],
n.d.[c] trace[c] 54%[c]
When electrooxidation of styrenes 1 with various
alcohols was carried out in the conditions of entry 6,
Table 3, bromohydrins ethers 6–8 were formed selec-
tively in 49–89% yields (Table 5).
2p, 36%[a], 46%[b], 2q, 34%[a], 30%[b], 2r, 26%[a], 26%[b],
91%[c]
53%[c]
29%[c]
The results in Table 5 show that the electrochemical
alkoxybromination successfully proceeds with styrenes
bearing both a halogen substituent in the aromatic ring
(6d, 85%) and electron-donating methyl group (6b,
85%). The reaction with α-methyl styrene 1h gave
product 6h in a high 86% yield. Using ethanol and iso-
propanol, bromohydrins ethers 7a and 8a were
obtained from styrene 1a in 72% and 49% yields
respectively (Table 5).
The proposed pathway of bromohydrins 2 forma-
tion via alkene 1 difunctionalization includes both
electrochemical and chemical stages. Scheme 3 illus-
trates the mechanism using the transformation of 1a
into 2a.
2s, 25%[a], 34%[b], 13%[c]
2s’, trace[a], 11%[b],
trace[c]
[a] Reaction conditions for Method A: undivided cell, glassy
carbon plate anode (15 mm×25 mm×2 mm), platinum plate
cathode (15 mm × 25 mm × 0.4 mm), constant current =
200 mA (j=53.3 mA/cm2), 4 F/mol, 1a–s (1 mmol,
68–197 mg), AcOH (5 mmol, 300 mg), KBr (5 mmol, 595 mg),
solvent system (DMSO/H2O=5 mL/5 mL), 50 C, air atmo-
°
sphere.
[b] Reaction conditions for Method B: 12 F/mol instead of 4 F/
mol.
[c] Reaction conditions for Method C: CF3COOH (5 mmol,
570 mg) and 12 F/mol instead of AcOH (5 mmol, 300 mg)
and 4 F/mol.
Molecular bromine is electrochemically generated
from the bromide anions on the anode surface,[38] and
then can be transformed into [Br]+[39] species. In
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generated bromine or [Br]+ species leads to cyclic
bromonium cation A. The side dibromide 4 is probably
obtained by the reaction of bromide with cyclic
bromonium cation A.[40] The reaction of styrene 1a
with the stabilized cation C leads to the sulfonium salt
B,[34] which can be also formed from the reaction of A
with DMSO.[13]
Table 5. Electrochemical synthesis of bromohydrins ethers 6–8
from alkenes 1.[a]
The water as the nucleophile can attack either the
bromonium ion A or the sulfonium salt B.[13,37] Both
reactions would afford the target product 2a. High
concentration of hydroxide ion can result in epoxide 3
formation possibly via cyclization of 2a.[33] The diol 5
could be formed from the subsequent nucleophilic
opening of epoxide 3.[41] The use of AcOH or TFA as
an additive lowers the hydroxide ion concentration. A
control experiment (see SI) confirms that epoxide 3
does not transform into bromohydrin 2a under our
optimized reaction conditions. Also, the radical mech-
anism of target product formation supposing several
reaction stages on the surface of the electrodes cannot
be completely excluded. The Br anion could be
oxidized at the anode into Br radical, which attached to
the styrene double bond, followed by anodic oxidation
of the benzyl radical to the cation and nucleophile
attack. Since we used high current density (j=
53.3 mA/cm2) and observed the bromine dripping off
the electrodes during the reaction the radical pathway
seems less likely.
6a, 89%
6h, 86%
6b, 78%
7a, 72%
6d, 85%
8a, 49%
[a] Reaction conditions: undivided cell, glassy carbon plate
anode (15 mm×25 mm×2 mm), platinum plate cathode
(15 mm×25 mm×0.4 mm), constant current=200 mA, 12
F/mol, 1a-d, 1h (1 mmol, 104–122 mg), AcOH (5 mmol,
300 mg), KBr (5 mmol, 595 mg), solvent system (CH3CN/
CH3OH or CH3CN/EtOH or CH3CN/i-PrOH=5 mL/5 mL).
The proposal about the anodic oxidation of bromide
is supported by CV data (Figures 1, 2), which
demonstrate that bromide anion is the only component
of the reaction mixture that undergoes oxidation (Fig-
ure 1); styrene 1a is not oxidized under these con-
ditions (Figure 2). Addition of styrene 1a into KBr
solution results in decreasing of reverse peak of
reduction (Figure 3). It can be explained by the
reaction of styrene 1a with the generated bromine
species.
Scheme 3. Proposed reaction mechanism on the example of the
formation of 2a from styrene 1a.
Figure 1. CV curve for a 0.1 M solution of KBr in 0.125 M
Bu4NBF4 in DMSO/H2O (3/1 vv) on a working glassy-carbon
electrode (d=3 mm) under a scan rate of 0.1 V/s (An enlarged
image of the section of CV from 0 to 1.6 V is in the center.).
addition, DMSO can react with the [Br]+ species to
form complex C.[34] The attack of the electrochemically
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of 2a formation and growth of 3 yield. The observed
result confirms the importance of the acid for slowing
down the epoxide formation in the electrochemically
induced bromohydrin synthesis from alkenes.
Conclusion
An effect of co-solvent and acid in the indirect
electrochemical transformations of alkenes was discov-
ered in this work. The addition of the co-solvent and
the acid into the well-known system “alkene, bromide
anion, ROH, electric current”, which previously led to
unselective chemistry, allows to selectively obtain
bromohydrins and their ethers. It illustrates the
unlimited possibilities of the electroorganic synthesis
reopened by the addition of counter-intuitive at first
glance reagents. Electrochemical synthesis of bromo-
hydrins and their ethers from alkenes in yields from
moderate to high was disclosed. The newly developed
electrochemical method is characterized by high
efficiency and experimental convenience, as it involves
an undivided electrochemical cell, high current den-
sities, and high concentration of starting reagents.
Figure 2. CV curve for a 0.1 M solution of 1a in 0.125 M
Bu4NBF4 in DMSO/H2O (3/1 vv) on a working glassy-carbon
electrode (d=3 mm) under a scan rate of 0.1 V/s.
Experimental Section
General Experimental Details
1H and 13C NMR spectra were recorded on Bruker AVANCE II
300 spectrometer (300.13 and 75.48 MHz, respectively) in
CDCl3. Chemical shifts were reported in parts per million
(ppm), and the residual solvent peak was used as an internal
reference: 1H (CDCl3 δ=7.26 ppm), 13C (CDCl3 δ=
77.16 ppm). Multiplicity was indicated as follows: s (singlet), d
(doublet), t (triplet), q (quartet), m (multiplet).
Figure 3. CV curve for a solution mixture of 1a (0.1 M) with
KBr (0.1 M) in 0.125 M Bu4NBF4 in DMSO/H2O (3/1 vv) on a
working glassy-carbon electrode (d=3 mm) under a scan rate
of 0.1 V/s.
High resolution mass spectra (HR-MS) were measured on a
Bruker micrOTOF II instrument using electrospray ionization
(ESI).[42] The measurements were performed in a positive ion
mode (interface capillary voltage – 4500 V); mass range from
m/z 50 to m/z 3000 Da; external calibration with Electrospray
Calibrant Solution (Fluka). A syringe injection was used for all
The additional evidence of the proposed mechanism
(Scheme 3) was received from the experiments with
various amounts of added acid and potassium
hydroxide (Scheme 4).
In the presence of 5 eq. AcOH, the target bromohy- acetonitrile solutions (flow rate 3 μL/min). Nitrogen was
°
applied as a dry gas; interface temperature was set at 180 C.
drin 2a was formed in an 86% yield. The formation of
epoxide 3 did not occur. Decreasing the acid amount
and increasing the hydroxide amount led to inhibition
Cyclic voltammetry (CV) was implemented on an IPC-Pro M
computer-assisted potentiostat manufactured by Econix (scan
rate error 1.0%; potential setting 0.25 mV; scan rate
100 mVsÀ 1). The experiments were performed in a 2 mL five-
neck glass conic electrochemical cell with a water jacket for
thermostatting. CV curves were recorded using a three-electrode
scheme. The working electrode was a disc glassy-carbon
electrode (d=3 mm). A platinum wire served as an auxiliary
electrode. An Ag/Ag+ electrode was used as the reference
electrode and was linked to the solution by a porous glass
diaphragm. The solutions were kept under thermally controlled
°
conditions at 50�0.5 C and deaerated by bubbling argon.
Electrochemical experiments were performed under an argon
atmosphere. The working electrode was polished before record-
Scheme 4. Control experiments.
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ing each CV curve. In a typical case, 2 mL of solution was
utilized. The compound concentration was 0.1 M.
(15 mm×25 mm×0.4 mm) and connected to a DC regulated
power supply. The solution of styrene 1a (1.0 mmol,
104.1 mg), acetic acid (5.0 mmol, 300.2 mg) and supporting
electrolyte KBr (5.0 mmol, 595.0 mg) in DMSO/H2O (5 mL/
The TLC analysis was carried out on standard silica gel
chromatography plates (DC-Fertigfolien ALUGRAMR Xtra SIL
G/UV254). Column chromatography was performed using silica
gel (0.060-0.200 mm, 60 A, CAS 7631-86-9, Acros).
5 mL) was electrolyzed using constant current conditions
2
°
(53.3 mA/cm ) at 50 C under magnetic stirring for 32 min with
I=200 mA. Then electrodes were washed with CH2Cl2 (2×
20 mL). The combined organic phases were washed with water
(3×15 mL) and dried over Na2SO4, filtered and concentrated
under reduced pressure using a rotary evaporator (15–20
Vinylbenzene (1a), 1-methyl-4-vinylbenzene (1b), 1-methyl-2-
vinylbenzene (1c), 1-fluoro-4-vinylbenzene (1d), 1-chloro-4-
vinylbenzene (1e), 1-(4-vinylphenyl)ethan-1-one (1f), 1-meth-
yl-3-vinylbenzene (1g), prop-1-en-2-ylbenzene (1h), 2-vinyl-
pyridine (1m), 3-methyl-2-(prop-1-en-1-yl)pyridine (1n), 1H-
indene (1o), cyclohexene (1q), cyclopentene (1r), allylbenzene
(1s), acetic acid, trifluoroacetic acid, HCO2H, HBr (48% aq),
H2SO4, KBr, NH4Br, Me4NBr, LiClO4, Na2SO4, CH3OH, THF,
DMSO, CH3CN, CH2Cl2, petroleum ether (PE, 40/70), ethyl
acetate (EA) were purchased from commercial sources and was
used as is.
°
mmHg), (bath temperature, ca. 20–25 C). Product 2a was
isolated by chromatography on SiO2 (PE:EtOAc=10:1).
Experimental Procedures for Table 3
Method A
An undivided cell was equipped with a glassy carbon anode
(15 mm×25 mm×2 mm) and
a
platinum plate cathode
Starting alkenes 1i,[43] 1j,[44] 1k,[45] 1l,[46] 1p,[47] were prepared
accordingly literature procedures.
(15 mm×25 mm×0.4 mm) and connected to a DC regulated
power supply. The solution of alkene 1a–s (1.0 mmol, 68.1–
197.1 mg), acetic acid (5.0 mmol, 300.2 mg) and supporting
electrolyte KBr (5.0 mmol, 595.0 mg) in solvent system
Experimental Procedure for Scheme 2
(DMSO/H2O=5 mL/5 mL) was electrolyzed using constant
2
°
An undivided cell was equipped with a glassy carbon anode
current conditions (53.3 mA/cm ) at 50 C under magnetic
(15 mm×25 mm×2 mm) and
a
platinum plate cathode
stirring for 32 min with I=200 mA. Then electrodes were
washed with CH2Cl2 (2×20 mL). The combined organic phases
were washed with water (3×15 mL) and dried over Na2SO4,
filtered and concentrated under reduced pressure using a rotary
(15 mm×25 mm×0.4 mm) and connected to a DC regulated
power supply. The solution of styrene 1a (1.0 mmol, 104.1 mg)
and supporting electrolyte KBr (5.0 mmol, 595.0 mg) in a H2O
°
(10 mL) was electrolyzed using constant current conditions
evaporator (15-20 mmHg), (bath temperature, ca. 20–25 C).
Product 2a-s was isolated by chromatography on SiO2 (PE:
EtOAc).
2
°
(53.3 mA/cm ) at 50 C under magnetic stirring for 32 or
64 min with I=200 mA. Then electrodes were washed with
CH2Cl2 (20 mL). The organic phases were washed with water
(15 mL) and dried over Na2SO4, filtered and concentrated under
reduced pressure using a rotary evaporator (15–20 mmHg),
Method B
°
(bath temperature, ca. 20–25 C). Products 2a, 3, 4, 5 were
isolated by chromatography on SiO2.
An undivided cell was equipped with a glassy carbon anode
(15 mm×25 mm×2 mm) and
a
platinum plate cathode
(15 mm×25 mm×0.4 mm) and connected to a DC regulated
power supply. The solution of alkene 1a–s (1.0 mmol, 68.1-
197.1 mg), acetic acid (5.0 mmol, 300.2 mg) and supporting
electrolyte KBr (5.0 mmol, 595.0 mg) in solvent system
General Experimental Procedure for Table 1
An undivided cell was equipped with a glassy carbon anode
(15 mm×25 mm×2 mm) and
a
platinum plate cathode
(DMSO/H2O=5 mL/5 mL) was electrolyzed using constant
2
°
(15 mm×25 mm×0.4 mm) and connected to a DC regulated
power supply. The solution of styrene 1a (1.0 mmol,
104.1 mg), acetic acid (5.0 mmol, 300.2 mg) and supporting
electrolyte KBr (5.0 mmol, 595.0 mg) in a solvent system
(H2O=10 mL or THF/H2O, CH3OH/H2O, CH3CN/H2O,
current conditions (53.3 mA/cm ) at 50 C under magnetic
stirring for 96 min with I=200 mA. Then electrodes were
washed with CH2Cl2 (2×20 mL). The combined organic phases
were washed with water (3×15 mL) and dried over Na2SO4,
filtered and concentrated under reduced pressure using a rotary
°
DMSO/H2O=5 mL/5 mL) was electrolyzed using constant
evaporator (15–20 mmHg), (bath temperature, ca. 20–25 C).
Product 2a–s was isolated by chromatography on SiO2 (PE:
EtOAc).
2
°
current conditions (53.3 mA/cm ) at 50 C under magnetic
stirring for 32 min with I=200 mA. Then electrodes were
washed with CH2Cl2 (2×20 mL). The combined organic phases
were washed with water (3×15 mL) and dried over Na2SO4,
filtered and concentrated under reduced pressure using a rotary
Method C
°
evaporator (15-20 mmHg), (bath temperature, ca. 20–25 C).
Product 2a was isolated by chromatography on SiO2 (PE:
EtOAc=10:1).
An undivided cell was equipped with a glassy carbon anode
(15 mm×25 mm×2 mm) and
a
platinum plate cathode
(15 mm×25 mm×0.4 mm) and connected to a DC regulated
power supply. The solution of alkene 1a-s (1.0 mmol, 68.1–
197.1 mg), trifluoroacetic acid (5.0 mmol, 371.0 μL) and
supporting electrolyte KBr (5.0 mmol, 595.0 mg) in solvent
General Experimental Procedure for Table 2
An undivided cell was equipped with a glassy carbon anode
system (DMSO/H2O=5 mL/5 mL) was electrolyzed using
2
°
(15 mm×25 mm×2 mm) and
a
platinum plate cathode
constant current conditions (53.3 mA/cm ) at 50 C under
Adv. Synth. Catal. 2021, 363, 1–10
7
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RESEARCH ARTICLE
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magnetic stirring for 96 min with I=200 mA. Then electrodes
were washed with CH2Cl2 (2×20 mL). The combined organic
phases were washed with water (3×15 mL) and dried over
Na2SO4, filtered and concentrated under reduced pressure using
a rotary evaporator (15-20 mmHg), (bath temperature, ca. 20–
Russo, Tetrahedron Lett. 1997, 38, 5843–5846; e) J.
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May, H. Gröger, Adv. Synth. Catal. 2007, 349, 2697–
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°
25 C). Product 2a-s was isolated by chromatography on SiO2
(PE:EtOAc).
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General Experimental Procedure for Table 4
An undivided cell was equipped with a glassy carbon anode
(15 mm×25 mm×2 mm) and
a
platinum plate cathode
(15 mm×25 mm×0.4 mm) and connected to a DC regulated
power supply. The solution of styrene 1a (1.0 mmol,
104.1 mg), acetic acid (5.0 mmol, 300.2 mg) or trifluoroacetic
acid (5.0 mmol, 570.1 mg) and supporting electrolyte KBr
(5.0 mmol, 595.0 mg) in solvent system (CH3OH=10 mL;
CH3CN/CH3OH or DMSO/CH3OH=5 mL/5 mL) was electro-
2
°
lyzed using constant current conditions (53.3 mA/cm ) at 50 C
under magnetic stirring for 32 min or 96 min with I=200 mA.
The reaction mixture was concentrated down to 3–4 mL
volume, and then dissolved in 40 mL CH2Cl2 which was washed
with water (2×15 mL) and dried over Na2SO4, filtered and
concentrated under reduced pressure using a rotary evaporator
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°
(15-20 mmHg), (bath temperature, ca. 20–25 C). Product 6a
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Experimental Procedure for Table 5
An undivided cell was equipped with a glassy carbon anode
(15 mm×25 mm×2 mm) and
a
platinum plate cathode
(15 mm×25 mm×0.4 mm) and connected to a DC regulated
power supply. The solution of alkene 1a-d, 1h (1.0 mmol,
104.1-122.1 mg), acetic acid (5.0 mmol, 300.2 mg) and support-
ing electrolyte KBr (5.0 mmol, 595.0 mg) in solvent system
(CH3CN/CH3OH or CH3CN/EtOH or CH3CN/i-PrOH=5 mL/
5 mL) was electrolyzed using constant current conditions
2
°
(53.3 mA/cm ) at 50 C under magnetic stirring for 96 min with
I=200 mA. The reaction mixture was concentrated down to 3–
4 mL volume, and then dissolved in 40 mL CH2Cl2 which was
washed with water (2×15 mL) and dried over Na2SO4, filtered
and concentrated under reduced pressure using a rotary
°
evaporator (15-20 mmHg), (bath temperature, ca. 20–25 C).
Product 6a, 6b, 6d, 6h, 7a, 8a was isolated by chromatog-
raphy on SiO2 (PE:EtOAc).
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Acknowledgements
This work was supported by the Russian Science Foundation
(Grant No 19-73-20190).
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RESEARCH ARTICLE
Alkene, Bromide, and ROH – How To Achieve Selectivity?
Electrochemical Synthesis of Bromohydrins and Their Ethers
Adv. Synth. Catal. 2021, 363, 1–10
O. V. Bityukov, V. A. Vil’, G. I. Nikishin, A. O. Terent’ev*