Reaction of Acyl Chlorides with in Situ Formed Zinc Selenolates: Synthesis of Selenoesters versus Ring-Opening Reaction of Tetrahydrofuran

Article abstract of DOI:10.1155/2016/2849140

Attempting to apply the in situ production of PhSeZnSePh to the synthesis of selenoesters, an unexpected reaction involving the solvent (tetrahydrofuran) was observed and studied. We reported here some evidences about the mechanism and the possibility to

Full text of DOI:10.1155/2016/2849140

Hindawi Publishing Corporation
Journal of Chemistry
Volume 2016, Article ID 2849140, 8 pages
http://dx.doi.org/10.1155/2016/2849140
Research Article
Reaction of Acyl Chlorides with In Situ Formed Zinc
Selenolates: Synthesis of Selenoesters versus Ring-Opening
Reaction of Tetrahydrofuran
Gemma Bellino,1 Marialaura Scisciani,1 Jaqueline Pinto Vargas,2
Luca Sancineto,1 Luana Bagnoli,1 Francesca Marini,1 Diogo Seibert Lüdtke,2
Eder Joao Lenardao,3 and Claudio Santi1
1Group of Catalysis and Organic Green Chemistry, Department of Pharmaceutical Sciences, University of Perugia,
Via del Liceo 1, 06100 Perugia, Italy
2
´
Instituto de Quımica, Universidade Federal do Rio Grande do Sul (UFRGS), Avenida Bento Gon¸calves 9500,
91501-970 Porto Alegre, RS, Brazil
3
´
´
ˆ
ˆ
´
ˆ
Laboratorio de Sıntese Organica Limpa (LASOL), Centro de Ciencias Quımicas, Farmaceuticas e de Alimentos (CCQFA),
Universidade Federal de Pelotas (UFPel), P.O. Box 354, 96010-900 Pelotas, RS, Brazil
Correspondence should be addressed to Claudio Santi; claudio.santi@unipg.it
Received 2 March 2016; Accepted 24 May 2016
Academic Editor: Matthias D’hooghe
Copyright © 2016 Gemma Bellino et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Attempting to apply the in situ production of PhSeZnSePh to the synthesis of selenoesters, an unexpected reaction involving the
solvent (tetrahydrofuran) was observed and studied. We reported here some evidences about the mechanism and the possibility to
control the chemoselectivity of this new reaction that afforded the formation of interesting selenoderivatives in which the selenium
moiety and the carboxylic one are spaced by four carbon units.
1. Introduction
affording in situ a seleno-zinc complex (in equilibrium with
the corresponding selenol) that can be conveniently used to
effect ring-opening reactions of aziridines [9] and epoxides,
as well as nucleophilic substitution [10] and hydroselenyla-
tion of alkynes [11] (Scheme 1). e novelty of this protocol is
mainly related to the simplicity of the procedure that prevents
the typical drawback of using volatile selenols, which has
a persistent smell. In this case, the selenol is formed in a
closed vial and immediately used for the reaction with the
electrophile. We also demonstrated that, in some cases, the
water and the organic phase can be recovered afer the first
reaction and directly reused as medium for further reactions,
maintaining good yields for 5–10 cycles. is aspect positively
impacts the overall sustainability of the reaction [12].
Given the continuous interest around the synthesis, the
reactivity, and the biological properties of organochalcogen
compounds and continuing our ongoing studies on the devel-
opment of new ecofriendly protocols for the selenenylation
of organic substrates, we investigated a new strategy for the
preparation of selenoesters [1–4].
e incorporation of selenium into organic compounds
can be conveniently achieved using nucleophilic reagents
such as selenols or selenolates, which can be generated in
situ via a reductive cleavage of the Se-Se bond starting
from a diselenide. Commonly used protocols for generating
selenolates involve the use of several reducing agents, such
as NaBH , LiAlH , and other expensive and ofen not easily
Starting from diphenyl diselenide, the discoloration of the
organic phase is an unequivocal indication of the complete
reduction of the Se-Se bond and the formation of the zinc
complex that, due to the presence of the hydrochloric acid,
4
4
handled metal sources [5–8].
We recently demonstrated that elemental zinc reduces
diselenides in acidic biphasic system (aq. 10% HCl/Et O)
2

2
Journal of Chemistry
H
N
coupling constants where applicable, number of hydrogen
atoms, and assignment where possible). Abbreviations are s
(singlet), d (doublet), t (triplet), q (quartet), quin (quintet),
sex (sextet), dd (doublet of doublet), dt (doublet of triplet),
ddt (doublet of doublet of triplet), m (multiplet), and br. s
(broad signal). Coupling constant (ꢁ) is quoted in hertz (Hz)
to the nearest 0.1 Hz. GC-MS analyses were carried out with
a HP-6890 gas chromatograph (dimethyl silicone column,
12.5 m) equipped with an HP-5973 mass-selective detector.
SePh
NH2
R
R
R
R
O
SePh
(PhSe)2
Et2O
H2O
PhSeH
ZnCl2
OH
[(PhCh)2Zn]
RX
R
HCl (10%)
2.1. General Procedures for the Synthesis of Selenoester in
Zn
PhSe
23∘C, 1h
Biphasic Conditions. Diphenyl diselenide (0.637 mmol) was
poured into a biphasic system composed of Et O (2 mL) and
2
H
H
HCl (aq. 10%, 2 mL) and zinc pellets (20 eq.) were added. e
mixture was vigorously stirred (800 rpm) in a closed vial until
discoloration of the organic layer (around 15 min).
R
R
SePh
Acyl chlorides 1a–g (1.274 mmol) were added and the
mixture was stirred at room temperature for 4 h. e organic
phase was diluted with EtOAc (2 mL), separated, dried with
Na SO , and filtered and the solvent was removed under
vacuum. e products reported in Table 1 were purified by
flash chromatography on silica gel (PE/EtOAc: 96/4) and
characterized on the basis of 1H-NMR, 13C-NMR, and GC-
MS spectral analysis.
Scheme 1
2
4
is most reasonably in equilibrium with the corresponding
benzeneselenol.
During the attempts to apply this methodology to the
synthesis of selenol esters, starting from the corresponding
acyl chlorides, in order to avoid the presence of strong
hydrolytic conditions, we tested tetrahydrofuran (THF) as
solvent and triflic acid as anhydrous acidic catalyst for the
reduction. Serendipitously, we discovered that in these con-
ditions the ring-opening reaction of THF was favored. Ring-
opening reaction of cyclic tetrahydrofuran is an important
synthetic transformation because it affords a functionalized
4-carbon building block that can be used in many synthetic
applications including polymer chemistry. In addition, a
reaction able to break a carbon-oxygen bond of an ether
presents potentially useful applications in the decomposition
of polyether based polymers and, consequently, in the treat-
ment of the wastes for the production of new functionalized
chemicals [12–15].
2.2. General Procedure for the Synthesis of Selenoester in THF.
In a round bottom flask, containing diphenyl diselenide
(0.25 mmol) and zinc powder (0.458 mmol) in dry THF
(3 mL) under argon atmosphere, trifluoromethanesulfonic
acid (30 mol%) was added as the catalyst. e resulting
mixture was refluxed for 1 h, observing the formation of a
white suspension. Afer cooling to room temperature, the
acyl chloride (1a–g, 0.5 mmol) was added, and the mixture
was stirred for an additional 1.5 h at refluxing temperature.
e crude was then extracted with ethyl acetate (3x 10 mL)
and the organic layers were washed with brine (10 mL) and
dried over Na SO . Afer filtration, the organic solvent was
2
4
removed under reduce pressure. Products 3, 6, and 7 were
purified by flash chromatography on silica gel (PE/EtOAc:
96/4) and characterized by 1H-NMR and 13C-NMR spectra.
Physical and spectroscopic data of selected compounds
2. Materials and Methods
Reactions were conducted in round bottom flasks and were
stirred with Teflon-coated magnetic stirring bars. Solvents
and reagents were used as received unless otherwise noted.
Acyl chlorides 1a, 1d, and 1g were commercially available; acyl
chlorides 1b, 1c, 1e, and 1f were synthesized according to the
literature [16]. Analytical thin-layer chromatography (TLC)
was performed on silica gel 60 F254 precoated aluminum
foil sheets and visualized by UV irradiation or by iodine
staining. Silica gel Kieselgel 60 (70–230 mesh) was used for
column chromatography. NMR experiments were conducted
at 25∘C with a Bruker DPX 200 spectrometer operating at
200 MHz for 1H and 50.31 MHz for 13C, or with a Bruker DRX
spectrometer operating at 400 MHz for 1H and 100.62 MHz
are reported below.
1
Se-phenyl benzoselenoate (2a): H-NMR (CDCl ,
3
200 MHz): ꢀ = 7.96–7.92 (m, 2H, H-Ar), 7.63–7.42 (m, 8H,
H-Ar) ppm. 13C-NMR (CDCl , 50 MHz): ꢀ = 193.5, 138.5,
3
136.4, 133.9, 129.4, 129.1, 128.9, 127.4, 125.8 ppm. GC-MS: m/z
(%) = 262 (1) [M+], 157 (5), 105 (100), 77 (50), 51 (14).
1
Se-phenyl 2-bromobenzoselenoate (2b): H-NMR (CDCl ,
3
200 MHz): ꢀ = 7.72–7.6 (m, 4H, H-Ar), 7.45–7.34 (m, 5H, H-
Ar) ppm. 13C-NMR (CDCl , 50 MHz): ꢀ = 194.4, 140.6, 135.8,
3
134.3, 132.6, 129.5, 129.2, 128.8, 127.3, 126.6, 118.0 ppm. GC-MS:
m/z (%) = 340 (1) [M+], 232 (3), 183 (100), 157 (54), 76 (16), 50
(9).
1
Se-phenyl 4-butylbenzoselenoate (2c): H-NMR (CDCl ,
3
for 13C experiments.
200 MHz): ꢀ = 7.85 (d, J = 8.1 Hz, 2H, H-Ar), 7.61–7.57 (m, 2H,
1H and 13C chemical shifs (ꢀ) are reported in parts per
H-Ar), 7.44–7.41 (m, 3H, H-Ar), 7.31–7.26 (m, 2H, H-Ar), 2.67
million (ppm), relative to TMS (ꢀ = 0.0 ppm) and the residual
(t, J = 7.8 Hz, 2H, CH ), 1.61 (quin, J = 8.15 Hz, 2H, CH ), 1.36
2
2
solvent peak of CDCl (ꢀ = 7.26 and 77.00 ppm in 1H and 13
C
(sex, J = 7.6 Hz, 2H, CH ), 0.95 (t, J = 7.2 Hz, 3H, CH ) ppm.
3
2
3
NMR, resp.). Data are reported as chemical shif (multiplicity,
13C-NMR (CDCl , 100 MHz): ꢀ = 192.7, 149.8, 136.4, 136.2,
3

Journal of Chemistry
Table 1: Scope of the reaction (see Scheme 2).
3
(E)-Se-phenyl 3-phenylprop-2-eneselenoate (2f ): 1H-NMR
(CDCl , 200 MHz): ꢀ = 7.58–7.54 (m, 5H, H-Ar), 7.43–7.40
3
Entry
(m, 6H, H-Ar), 6.78 (d, J = 15 Hz, 1H, CH) ppm. 13C-NMR
R
1a
1b
1c
Yield% of 2
(CDCl , 50 MHz): ꢀ = 190.8, 141.1, 135.9, 133.9, 130.9, 129.4,
3
129.1, 129.0, 128.6, 128.1, 126.3 ppm. GC-MS: m/z (%) = 288 (1)
[M+], 157 (14), 131 (100), 103 (55), 77 (36).
1
37
Se-phenyl 2-phenylethaneselenoate (2g): 1H-NMR
(CDCl , 200 MHz): ꢀ = 7.45–7.35 (m, 2H, H-Ar), 7.34–7.26
3
(m, 8H, H-Ar), 3.88 (s, 2H, CH ) ppm. 13C-NMR (CDCl ,
2
3
50 MHz): ꢀ = 198.9, 135.8, 132.6, 130.1, 129.3, 128.9, 128.8, 127.8,
126.6, 53.6 ppm. GC-MS: m/z (%) = 276 (10) [M+], 157 (22),
119 (26), 91 (100), 65 (26).
2
3
52
84
Br
1
4-(Phenylselanyl)butyl benzoate (5a): pale oil; H-NMR
(CDCl , 200 MHz): ꢀ = 7.99–7.94 (m, 2H, H-Ar), 7.48–7.35
3
(m, 5H, H-Ar), 7.21–7.18 (m, 3H, H-Ar), 4.27 (t, J = 5.5 Hz,
2H, CH -O), 2.92 (t, J = 6.3 Hz, 2H, CH -Se), 1.90–1.78 (m,
2
2
4H, CH ) ppm. 13C-NMR (CDCl , 50 MHz): ꢀ = 166.5, 132.8,
2
3
132.6, 130.2, 129.9, 129.5, 128.9, 128.3, 126.8, 64.2, 28.7, 27.3,
O2N
26.6 ppm.
4-(Phenylselanyl)butyl 2-bromobenzoate (5b): pale oil; 1H-
Mixture of
unidentified
compounds
4
NMR (CDCl , 200 MHz): ꢀ = 7.69 (m, 2H, H-Ar), 7.49 (m,
3
2H, H-Ar), 7.35–7.22 (m, 5H, H-Ar), 4.33 (t, J = 5.7 Hz, 2H,
CH -O), 2.96 (t, J = 6.7 Hz, 2H, CH -Se), 1.9–1.85 (m, 4H,
NO2
2
2
1d
CH ) ppm. 13C-NMR (CDCl , 100 MHz): ꢀ = 166.2, 134.3,
2
3
S
132.7, 132.5, 132.4, 131.2, 130.0, 129.1, 127.1, 126.9, 121.6, 64.9,
5
6
23
0
28.6, 27.3, 26.7 ppm.
4-(Phenylselanyl)butyl 4-butylbenzoate (5c): pale oil; 1H-
1e
NMR (CDCl , 200 MHz): ꢀ = 7.9 (d, J = 8.03, 2H, H-Ar),
3
7.5–7.47 (m, 2H, H-Ar), 7.25–7.22 (m, 5H, H-Ar), 4.3 (t, 2H,
CH O), 2.96 (t, 2H, CH Se), 2.66 (t, J = 8 Hz, 2H, CH ), 1.94–
2
2
2
1.87 (m, 4H, CH ), 1.61–1.53 (m, 2H, CH ), 1.37–1.30 (m, 2H,
2
2
1f
CH ), 0.93 (t, J = 7.16 Hz, 3H, CH ) ppm. 13C-NMR (CDCl ,
2
3
3
100 MHz): ꢀ = 166.6, 148.5, 132.7, 130.1, 129.6, 129.0, 128.5, 127.7,
126.8, 64.06, 35.7, 33.3, 28.8, 27.4, 26.2, 22.3, 13.9 ppm.
4-(Phenylselanyl)butyl thiophene-2-carboxylate (5e): pale
7
0
1g
oil; 1H-NMR (CDCl , 200 MHz): ꢀ = 7.76 (dd, J = 1.18, 3.72 Hz,
3
1H, H-Ar), 7.56–7.47 (m, 3H, H-Ar), 7.25–7.22 (m, 3H, H-Ar),
7. 09 (dd, J = 3.78, 4.96 Hz, 1H, H-Ar), 4.29 (t, J = 6 Hz, 2H,
CH ), 2.96 (t, J = 6.7 Hz, 2H, CH ), 1.92–1.80 (m, 4H, CH )
O
O
(PhSe)2 + Zn0
2
2
2
ppm. 13C-NMR (CDCl , 100 MHz): ꢀ = 162.2, 133.8, 133.3,
R
SePh
R
Cl
3
10% HCl, Et2O
2
1
23∘C, 4h
132.7, 132.3, 130.0, 129.05, 127.7, 126.8, 64.5, 28.7, 27.3, 26.6 ppm.
1
4-(Phenylselanyl)butyl 2-phenylacetate (5g): pale oil; H-
Scheme 2
NMR (CDCl , 200 MHz): ꢀ = 7.5–7.45 (m, 2H, H-Ar), 7.37–
3
7.23 (m, 8H, H-Ar), 4.09 (t, J = 6.1 Hz, 2H, CH O), 3.6 (s,
2
2H, CH ), 2.89 (t, J = 6.9 Hz, 2H, CH Se), 1.8–1.7 (m, 4H,
2
2
CH ) ppm. 13C-NMR (CDCl , 100 MHz): ꢀ = 171.6, 134.03,
129.3, 129.0, 127.5, 126.0, 35.8, 33.1, 22.3, 13.9 ppm. GC-MS: m/z
2
3
(%) = 318 [M+], 161 (100), 91 (30).
132.7, 130.1, 129.25, 129.1, 128.6, 127.1, 126.9, 64.25, 41.4, 28.6,
1
27.3, 26.5 ppm.
Se-phenyl 3,5-dinitrobenzoselenoate (2d): H-NMR
4-(4-(Phenylselanyl)butoxy)butyl benzoate (6a): pale oil;
(CDCl , 200 MHz): ꢀ = 9.28 (t, J = 2.05 Hz, 1H, H-Ar),
3
1H-NMR (CDCl , 200 MHz): ꢀ = 8.07–8.02 (m, 2H, H-Ar),
9.04 (d, J = 2.06 Hz, 2H, H-Ar), 7.7–7.4 (m, 5H, H-Ar) ppm.
3
13C-NMR (CDCl , 50 MHz): ꢀ = 190.4, 148.9, 141.5, 136.1,
7.56–7.4 (m, 5H, H-Ar), 7.26–7.22 (m, 3H, H-Ar), 4.33 (t, J =
6.38 Hz, 2H, CH O), 3.93 (dt, ꢁ = 6.02 Hz, ꢁ = 6.2 Hz, 4H,
3
130.07, 129.9, 126.7, 124.1, 122.6 ppm.
CH ), 2.93 (t, J = 7.1 Hz, 2H, CHdSe), 1.86–1.67 (m, 8H, CH )
2
t
1
Se-phenyl thiophene-2-carboselenoate (2e): pale oil; H-
2
2
2
ppm. 13C-NMR (CDCl , 50 MHz): ꢀ = 166.6, 132.9, 132.45,
NMR (CDCl , 200 MHz): ꢀ = 7.88 (dd, J = 1.2, 3.9 Hz, 1H, H-
3
3
130.45, 130.4, 129.5, 129.0, 128.3, 126.7, 70.2, 64.8, 29.8, 27.7,
26.9, 26.4, 25.6 ppm.
Ar), 7.71 (dd, J = 1.2, 4.96 Hz, 1H, H-Ar), 7.63–7.58 (m, 2H, H-
Ar), 7.44–7.41 (m, 3H, H-Ar), 7.17 (dd, J = 3.9, 4.96 Hz, 1H, H-
Ar) ppm. 13C-NMR (CDCl , 50 MHz): ꢀ = 183.6, 143.1, 136.3,
4-(4-(Phenylselanyl)butoxy)butyl 2-bromobenzoate (6b):
3
pale oil; 1H-NMR (CDCl , 200 MHz): ꢀ = 7.8–7.63 (m, 2H, H-
133.7, 132.0, 129.4, 129.2, 128.0, 125.5 ppm. GC-MS: m/z (%) =
3
268 (1) [M+], 157 (16), 111 (100), 83 (20).
Ar), 7.5–7.22 (m, 7H, H-Ar), 4.35 (t, J = 6.29 Hz, 2H, CH O),
2

4
Journal of Chemistry
Table 2: Preliminary results (see Scheme 4).
3.42 (dt, ꢁ = 5.7 Hz, ꢁ = 6.18 Hz, 4H, CH ), 2.92 (t, J =
7. 2 Hz, 2H,dCH Se), 1.84–1.67 (m, 8H, CH ) ppm. 13C-NMR
t
2
2
2
Ratios by
1H-NMR
(CDCl , 100 MHz): ꢀ = 166.3, 134.3, 132.5, 132.4, 132.37, 131.2,
mol% of
acid
3
Entry
ꢂ1
ꢂ2
ꢃ
128.9, 127.1, 126.7, 121.5, 70.2, 70.16, 65.5, 29.8, 27.7, 26.9, 26.3,
25.5 ppm.
2a
26
38
36
32
42
5a
48
34
38
42
38
6a
26
28
26
26
20
1
1 h
1 h
3 h
3 h
rt
rt
60
30
60
30
30
4-(4-(Phenylselanyl)butoxy)butyl thiophene-2-carboxylate
(6e): pale oil; 1H-NMR (CDCl , 200 MHz): ꢀ = 7.79 (dd, J =
2
3
4
5
3
1 h 1 h 30ꢀ Reflux
1 h 1 h 30ꢀ Reflux
6 h 1 h 30ꢀ Reflux
1.2, 3.7 Hz, 1H, H-Ar), 7.55 (m, 3H, H-Ar), 7.26 (m, 3H, H-
Ar), 7.09 (dd, J = 3.74, 4.98 Hz, 1H, H-Ar), 4.3 (t, J = 6.25, 2H,
CH O), 3.42 (dt, ꢁ = 5.29 Hz, ꢁ = 6.2 Hz, 4H, CH ), 2.92 (t, J
= 7.1 Hz, 2H, CH Se), 1.83–1.65 t(m, 8H, CH ) ppm. 13C-NMR
2
d
2
2
2
(CDCl , 100 MHz): ꢀ = 162.3, 133.9, 133.3, 132.5, 132.2, 130.4,
3
129.1, 128.9, 127.7, 126.7, 70.2, 64.9, 29.8, 29.7, 27.7, 26.9, 26.3,
25.6 ppm.
(PhSe)2
aq. 10% HCl
Zn0
Et2O
4-(4-(Phenylselanyl)butoxy)butyl 2-phenylacetate (6g):
1
O
O
pale oil; H-NMR (CDCl , 200 MHz): ꢀ = 7.51–7.47 (m, 2H,
[
PhSeZnSePh
]
3
3
R㰀
R㰀
Cl
PhSeZnCl
H-Ar), 7.33–7.24 (m, 8H, H-Ar), 4.1 (t, J = 6.05 Hz, 2H,
CH O), 3.62 (s, 2H, CH ), 3.38 (dt, ꢁ = 2.3 Hz, ꢁ = 6.1 Hz,
+
SePh
+
2
4
1
2
2
d
t
4H, CH ), 2.93 (t, J = 6.8 Hz, 2H, CH Se), 1.8–1.55 (m, 8H,
2
2
CH ) ppm. 13C-NMR (CDCl , 100 MHz): ꢀ = 172.0, 134.1,
O
2
3
132.5, 130.5, 129.25, 129, 128.5, 127.05, 126.7, 70.2, 64.7, 41.5,
28.8, 27.7, 26.9, 26.2, 25.5 ppm.
R㰀
Cl
1
O
3. Results and Discussion
R㰀
SePh
2
Afer the zinc mediated reduction of diphenyl diselenide in
the biphasic system composed by a 1 : 1 mixture of 10% aq.
HCl and diethyl ether (2 mL), 1 equivalent of the acyl chloride
1a–g was added and the mixture was stirred in a closed
vial for 4 h. e results reported in Table 1 evidenced that
the nucleophilic acyl substitution proceeded in moderated
to good yields only in the case of aryl carboxylic derivatives
1a-c and 1e and not in the case of vinyl (1f) or alkyl (1g)
analogues. Starting from substrates bearing functional group
susceptible to reductive conditions (1d), a complex mixture
of unidentified compounds was obtained.
e proposed mechanism for the reaction is reported in
Scheme 3. e zinc-selenolate 3, originated by reduction of
diphenyl diselenide, attacks the carbonyl group promoting
the nucleophilic substitution of the chloro atom. From this
reaction, the formation of a molecule of PhSeZnCl 4 can be
speculated. is reagent has been proven to be an effective
nucleophile for the synthesis of selenoesters in “on water
conditions” [17].
Scheme 3
and the selenium are spaced by one (5a) or two (6a) 4-carbon
units deriving from the ring opening of THF (Scheme 4).
Changes on the acid amount, the ꢂ2, as well as the reaction
temperature ꢃ, did not produce evident effect on the ratios
between selenoester 2a and the side products 5a and 6a
(Table 2, entries 1–4).
Interestingly, also a strong increment of ꢂ1 (from 1 h to 6 h)
did not produce effect on the products ratio, clearly indicating
that the ring-opening process did not occur during this time
but it is, reasonably, a concerted mechanism that involves
both the selenium nucleophile 3 and the electrophilic 1a.
Using the best reaction conditions reported in Table 2,
entry 4, we explored the reactivity of acyl chlorides 1a–g and
the results are summarized in Table 3.
In all the cases, the ratios were calculated by 1H-NMR of
the crude. Yields are referred to the overall isolated products
afer purification by flash chromatography. All the structures
were assigned based on 1H-NMR and 13C-NMR analysis.
In some cases, (Table 3, entries 1, 3, 5, and 7), both
side products (5 and 6) were observed in a comparable
amount with respect to the selenol ester 2. In the case of the
electron rich acyl chloride 1c, the yield of selenol ester 2c
was lower (34%) and only 5c was formed as side product.
Interestingly, the reaction from the strongly electrophilic 1d
afforded quantitatively the target compound 2d. e chloride
of the cinnamic acid 1f confirmed a scarce reactivity affording
2f only in 20% yield associated with the chlorine derivative 7f
(Scheme 5).
With the only exception of 1d, in all the cases the only
side product observed was the carboxylic acid, indicating that
the hydrolysis strongly competes with the desired reaction.
With the aim to improve the yield of selenoesters 3 using
in the reaction model benzoyl chloride 1a, we changed the
conditions generating the selenium-zinc complex in THF
under the catalysis of trifluoromethanesulfonic acid (TfOH)
as anhydrous acid (Table 2, entry 1). Afer the formation of
the selenolate, which occurs during time ꢂ1, benzoyl chloride
1a was added and stirred for the additional time ꢂ2. e entire
reaction was performed at the same temperature indicated in
Table 2.
Surprisingly, beside the desired product, we observed the
formation of side compounds in which the carboxylic moiety

Journal of Chemistry
5
O
O
Zn0 powder
CF3SO3Hcat
O
Ph
Se
Cl
+
Ph
O
1a
PhSeSePh
[(PhSe)2Zn]
Ph
Se
2a
THF, T, t2
THF
3
5a
reflux, t1
O
O
Se
+
Ph
O
6a
Scheme 4
Table 3: Scope of the reaction in THF (see Scheme 5).
Ratio
Entry
Yield
R
2
5
6
7
1
60%
60%
50%
32
63
68
42
23
32
26
—
—
—
1a
1b
2
3
14
Br
—
n-Bu
1c
O2N
4
100%
100
—
—
—
NO2
1d
S
5
6
64%
24%
34
83
47
—
19
—
7
1e
—
1f
7
78%
80
15
5
—
1g
In order to verify if chloride intermediate 7 is involved
in the formation of 5 and 6 or if it is formed through
a parallel mechanism based on the nucleophilicity of the
chloride anion, 7a was prepared according to the procedure
reported by Enthaler and Weidauer [18] reacting benzoyl
Afer isolation of 7a, it was reacted with a preformed
suspension of 3, following the condition reported in Table 2,
entry 4, for the second part of the reaction (time ꢂ2). e
NMR analysis of the crude evidenced the formation of 5a
only in traces, confirming that, in the principal mechanism,
chloride 7 is not the precursor of products 5 and 6.
chloride 1a and ZnCl in THF (Scheme 6).
2

6
Journal of Chemistry
O
Zn0 powder
CF3SO3Hcat
O
R
Cl
O
O
1a–g
Cl
R
+
[(PhSe)2Zn]
PhSeSePh
O
THF
THF
R
R
Se
reflux, 1h 30㰀
3
reflux, 1h
2a–g
7f
Se
+
O
O
5a–g
O
O
Se
+
R
6a–g
Scheme 5
O
O
Cl
ZnCl2
O
O
Cl
+
Neat
80∘C, 24h
[9]
7a
1a
PhSeZnSePh
3
(PhSe)2 + Zn
TfOHcat THF reflux
80∘C, 2h
O
O
Se
5a
Only traces
Scheme 6
All these evidences suggested a concerted mechanism in
and the reaction conditions. e presence of zinc and the
strong hydrolytic conditions limit the scope of the reaction.
Performing the reaction in refluxing THF, the ring-opening
reaction of the solvent competes with the acyl substitution
and it was not possible to find conditions to improve the
selectivity of the process. Nevertheless, the reaction in THF
resulted in being effective for some substrates that failed
in the biphasic system (1d, 1f, and 1g). In addition, the
possibility of using this process to depolymerize polyether
based materials is an attracting and promising prospective
that is currently under investigation exploring the possibility
of transforming wastes in highly functionalized selenium
containing chemicals.
which three parallel reactions can be envisioned.
Zinc-selenolate complexes 3 or 4 can attack directly
acyl chloride affording the selenoesters 2 (black path in
Scheme 7). Alternatively, the same complexes, which rea-
sonably in THF solution coordinate one or two molecules
of solvent, attack the carbon of THF and the nucleophilic
oxygen can be immediately quenched by the electrophile
1, affording 5 (red path in Scheme 7), or open a second
molecule of THF and then react with acyl chloride 1 to afford
6 (green path in Scheme 7). From the PhSeZnCl 4, a similar
mechanism can be activated by the chloride, producing the
ester 7 (blue path in Scheme 7).
4. Conclusions
Competing Interests
In conclusion, we demonstrated that aqueous or anhydrous
acidic conditions can be used to activate the zinc mediated
reduction of diphenyl diselenide. e corresponding zinc-
selenolate complex has been studied toward the reaction with
a series of acyl chloride affording the corresponding selenol
esters in moderate to good yields depending on the substrate
e authors declare that there is no conflict of interests.
Authors’ Contributions
Gemma Bellino and Marialaura Scisciani contributed equally
to this work.

Journal of Chemistry
7
O
O
Se
Cl
R
O
R
O
5
7
Cl
Cl
R
1
R
1
Cl
R
1
O
O
O
O
O
O
PhSeZnCl
O
ClZnCl
PhSeZnSePh
3
4
O
R
R
Cl
1
Cl
1
O
R
Se
2
R
Cl
O
O
Se
O
R
O
O
O
1
6
PhSeZnSePh
or
3
4
Scheme 7
Acknowledgments
[3] C. Santi, C. Tidei, C. Scalera, M. Piroddi, and F. Galli, “Selenium
containing compounds from poison to drug candidates: a
review on the GPx-like activity,” Current Chemical Biology, vol.
7, no. 1, pp. 25–36, 2013.
Financial support from the Dipartimento di Scienze Far-
maceutiche, Universita` degli Studi di Perugia “Fondo per il
sostegno della Ricerca di Base 2015,” and Fondazione Cassa
di Risparmio di Perugia (2014.01000.021) are acknowledged.
e authors thank Regione Umbria, project “POR Umbria
2007–2013,” for the fellowship to Luca Sancineto. Eder Joao
Lenardao is Bolsista CAPES—Processo no. BEX 6391/14-1
and Mrs. Vargas was in CAPES Sandwich program with
a Doctorate scholarship (PDSE process 99999.001342/2014-
02). is research was undertaken as part of the scientific
activity of the international multidisciplinary “SeS Redox and
Catalysis” network.
[4] A. Pacula, F. Mangiavacchi, L. Sancineto, E. J. Lenardao, J.
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