Facile aerobic photo-oxidative synthesis of sulfinic esters

Article abstract of DOI:10.5562/cca3401

A mild and efficient one-pot visible light-induced method has been developed for the synthesis of sulfinic esters. Sulfinic esters are important structural elements that are frequently found in pharmaceutical agents and biologically active natural products. The routine procedure in the drug discovery and development process to prepare and fully characterize sulfinic esters make them a drug candidate for biological evaluation.

Full text of DOI:10.5562/cca3401

O R I G I NA L S C I E N T I F I C P A P E R
Croat. Chem. Acta 2018, 91(3), 383–387
Published online: September 24, 2018
DOI: 10.5562/cca3401
Facile Aerobic Photo-Oxidative Synthesis of
Sulfinic Esters
Pravin K. Singh,1 Praveen P. Singh,2 Vishal Srivastava1,*
1
2
Department of Chemistry, CMP Degree College, University of Allahabad, Allahabad - 211002, India
Department of Chemistry, United College of Engineering & Research, Naini, Allahabad - 211010, India
Corresponding author’s e-mail address: vishalgreenchem@gmail.com
*
RECEIVED: July 9, 2018
REVISED: September 3, 2018
ACCEPTED: September 4, 2018
Abstract: A mild and efficient one-pot visible light-induced method has been developed for the synthesis of sulfinic esters. Sulfinic esters are
important structural elements that are frequently found in pharmaceutical agents and biologically active natural products. The routine
procedure in the drug discovery and development process to prepare and fully characterize sulfinic esters make them a drug candidate for
biological evaluation.
Keywords: eosin Y, photoredox, sulfinic esters, SET, aerobic.
increasing focus on the utilization of visible light energy is
due to its chief, easily available, abundant nature and its
INTRODUCTION
ULFONIC esters constitute an important class of or-
ganic compound and its application have evoked con-
impeccable tolerance towards the environment.14 Harvest-
ing visible light and performing chemical reactions via
photocatalysis is one of the emerging strategies to meet
the increasing demand for more sustainable chemical pro-
cesses.15 Visible light photoredox catalysis (VLPC) has been
successfully applied to various organic transformations,
including aza-Henry reaction,16 cycloaddition,17 asymmetric
alkylation,18 [2+2] Diels-Alder reaction,19 oxidations,20
reductive dehalogenation21 etc. Photoredox catalysis is an
attractive approach to activating organic molecules by
translating visible light energy via single-electron transfer
(SET). Some pioneering researchers have dedicated to con-
S
siderable attention during past decades because of their
wide range of industrial pharmaceutical and biological
activities such as regulating them mitochondrial function of
the Parkinsonism protein DJ-11 and stimulating the glucose
uptake in muscle cells.2 Furthermore, sulfinic esters3 acts as
both electrophiles and nucleophiles, which have been
extensively employed for the synthesis of a variety of func-
tional products such as, α,β-unsaturated ketones,4 sulfon-
ylmethyl isonitriles,5 sulfinamides and sulfonamides,6
sulfoxides,7 sulfonimidamides,8 and sulfonyl allenes.9 Due
to the interesting applications, the development of alterna-
tive approaches to access sulfinic esters is of high im-
portance in synthetic chemistry. A wide array of sulfinic
esters were efficiently afforded in an exclusive chemoselec-
tive manner.10
verting solar energy into chemical energy for chemical
22,23
transformations
which includes a promising strategy
for the application of photoredox catalysts to initiate single
electron transfer processes have been developed.24,25
Previously, transition metal based photocatalysts were
widely used, which exhibit any one or more disadvantages
such as high cost, low sustainability and potential toxicity.
In recent year, eosin Y, fluorescein, rose bengal, nile red,
perylene and rhodamine B have been used as superior an
alternative to transition metal photoredox catalyst Ru (II)
and Ir(II) complexes as economically and ecologically
The challenge in chemistry to develop practical pro-
cess, reaction media, conditions and/or utility of materials
based on the idea of integrated chemical process is one of
the important issues in scientific society.11,12 The develop-
ment of environmentally benign processes is the goal of
synthetic organic chemistry.13 Rational approach involving
This work is licensed under a Creative Commons Attribution 4.0 International License.

384
P. K. SINGH et al.: Facile aerobic photo-oxidative synthesis …
superior surrogates in visible-light promoted organic trans-
formations involving SET26–29 (single electron transfer).
These organic dyes have got much more attention
because of ease of handling, eco-friendly and have great
potential for applications in visible-light-mediated organic
synthesis30–33 which fulfils the basic principle of green
chemistry.
Oxidation is the foundation of synthetic organic
chemistry, and recent methodology using molecular oxygen
is one way consistent with this notion due to its high atomic
effect or low E-factor as an oxidant. With this background in
mind, and in continuation of our research work34–41 for the
development of new synthetic methodology, we have
developed visible light promoted an aerobic photoox-
idative esterification of (hetero) aryl and alkyl thiols with
alcohols using Eosin Y at room temperature with merits of
mild reaction conditions, broad substrate scope,
operational simplicity and good functional group
tolerance.
The reaction gave the desired thioester 3(a–r) and
following this methodology, a series of control experiments
were performed, which indicates that the aerobic condition
is essential to give the desired product with high yield
(97 %) (Table 1, entry 1). There was no product formation
or it was formed in traces in the absence (–) of any one of
the reagents / catalyst (Table 1, entries 2–4). The reaction
did not proceed satisfactorily when a household 20 W
fluorescent lamp was used instead of green LEDs (Table 1,
entries 5 versus 1). Notably, the same result was obtained
on using O2 (balloon) instead of an air atmosphere (Table 1,
entry 7 versus 1), where as in the absence of any gas or
under a nitrogen atmosphere no product formation was
detected (Table 1, entry 4, 6). These results establish that
visible light, photocatalyst and air all are essential (+) for
the reaction and support the visible light promoted
photocatalytic model of the reaction.
The substituents on the aryl ring of aryl thiols influ-
enced the desired product yields to some extent. In gen-
eral, substrates 1 bearing an electron-donating group are
able to afford relatively higher yields than those of elec-
tron-deficient ones due to the fact that electron-rich aryl
thiols are beneficial to form more stable radical intermedi-
ates, thus favoring the coupling process. Interestingly, the
less-reactive heterocyclic substrates such as furan-3-thiol
1k and thiophene-2-thiol 1l were also amenable to the
transformation to afford the desired products in good
yields (3k, 3l). Further, the change of methanol to ethanol,
propyl alcohol, butyl alcohol, isopropanol and benzyl alco-
hol also led to the generation of desired sulfinic ester prod-
ucts at slightly different time duration (3m, 3n, 3o, 3p, 3q
and 3r). Furthermore, a variety of functional groups such as
–Me, –OMe, iso-propyl, –F, –Cl and –Br are well tolerated
in the transformation, which would offer the potential for
molecular complexity via further transformations.
RESULTS AND DISCUSSION
In order to work out the envisaged protocol, a key reac-
tion was conducted with thiol 1(a–r) and alcohol 2(a–r) in
2 mol % of eosin Y under an aerobic atmosphere (without
air bubbling) by irradiation with visible light (green light-
emitting diodes (LEDs), λmax = 535 nm) at rt.
Table 1. Screening and control experiments.(a)
Entry
On the basis of the above observations and the liter-
ature precedents, a plausible mechanism involving photo-
redox catalysis for the oxidative esterification to form
sulfinic ester is depicted in Scheme 1. On absorption of vis-
ible light, the organophotoredox catalyst eosin Y (EY) is ex-
1
2
3
4
5
6
7
8
+
–
+
+
+
+
+
+
+
+
–
+
+
+
+
+
+
+
30
120
120
120
30
97
n.r.(c)
n.r.
+
–
n.r.
1
cited to its singlet state EY* which through inter system
crossing (ISC) comes to its more stable triplet state 3EY* and
undergoes a single electron transfer (SET).3EY* may un-
dergo both reductive and oxidative quenching42–46 to gen-
erate RS• A, which undergo SET to give RSO• B. The coupling
of A and B gave the desired product. The single electron
transfer that generate the sulfur radicals were supported
by trapping of this radical by 2,2,6,6-tetramethylpiperidinyl
1-oxyl (TEMPO) as a radical scavenger.47 The formation of
superoxide radical anion (O2• −) during the reaction was
confirmed by the detection of the resulting H2O2 using KI/
starch indicator.48
+
45(d)
Trace
97
N2
O2
+
120
30
30
42(e)
(a)
Reaction conditions: thiol (1.0 mmol), eosin Y (2.0 mol %), alcohol
(3.0 mL), green LEDs [2.50 W, λ = 535 nm] irradiation under an air
atmosphere at rt.
Isolated yield of the product (3 a–r). n.r. = no reaction.
The reaction was carried out in the dark.
The reaction was carried out using 20 W CFL (compact fluorescent
lamp).
The reaction was carried out with 1.0 mol % of eosin Y.
(b)
(c)
(d)
(e)
Croat. Chem. Acta 2018, 91(3), 383–387
DOI: 10.5562/cca3401

P. K. SINGH et al.: Facile aerobic photo-oxidative synthesis …
385
Table 2. Scope of the reaction.
Entry
1
Product
Time / min Yield / %
Entry
10
Product
Time / min Yield / %
90
60
87
75
120
100
51
70
3j
3a
3b
2
3
11
12
3k
45
85
45
90
3l
3c
4
5
30
60
95
88
13
14
60
90
89
80
3m
3d
3n
3e
6
7
90
90
80
83
15
16
90
90
85
83
3f
3o
3p
3g
8
9
120
100
75
82
17
18
60
75
67
3q
3h
120
3r
3i
DOI: 10.5562/cca3401
Croat. Chem. Acta 2018, 91(3), 383–387

386
P. K. SINGH et al.: Facile aerobic photo-oxidative synthesis …
at room temperature. This protocol involves the use of
visible light as the cheapest and eco-sustainable reagents
as well as eosin Y as an organophotoredox catalyst at room
temperature. Thus, it is a superior alternative to the
existing method with respect to green and sustainable
chemistry (better atom- and step-economy) for redox
reactions.
Acknowledgment We sincerely thank the Emerging Science
Society for financial support as well as SAIF, CDRI, Lucknow,
and IISc, Bangalore, for providing microanalyses and
spectra.
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DOI: 10.5562/cca3401
Croat. Chem. Acta 2018, 91(3), 383–387