Eosin Y catalysed visible-light mediated aerobic oxidation of tertiary amines

Article abstract of DOI:10.1016/j.tetlet.2019.151041

A mild and efficient one-pot visible light-induced method has been developed for the aerobic oxidation of saturated carbon conjugated with pyridine moiety with an important conversion in medicinal and synthetic organic chemistry. This eosin Y based organi

Full text of DOI:10.1016/j.tetlet.2019.151041

Journal Pre-Proof
Eosin Y catalysed visible-light mediated aerobic oxidation of tertiary amines
Vishal Srivastava, Pravin K. Singh, Praveen P. Singh
PII:
S0040-4039(19)30798-1
DOI:
https://doi.org/10.1016/j.tetlet.2019.151041
TETL 151041
Reference:
Tetrahedron Letters
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Accepted Date:
1 July 2019
9 August 2019
11 August 2019
Please cite this article as: Srivastava, V., Singh, P.K., Singh, P.P., Eosin Y catalysed visible-light mediated aerobic
oxidation of tertiary amines, Tetrahedron Letters (2019), doi: https://doi.org/10.1016/j.tetlet.2019.151041
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Graphical Abstract
Eosin Y catalysed visible-light mediated
aerobic oxidation of tertiary amines
Vishal Srivastavaa Pravin K. Singha and Praveen P. Singh*b
Leave this area blank for abstract info.

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Tetrahedron Letters
Eosin Y catalysed visible-light mediated aerobic oxidation of tertiary amines
Vishal Srivastavaa , Pravin K. Singha and Praveen P. Singhb, 
aDepartment of Chemistry, CMP Degree College, University of Allahabad, Prayagraj 211002, India
bDepartment of Chemistry, United College of Engineering & Research, Naini, Prayagraj 211010, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A mild and efficient one-pot visible light-induced method has been developed for the aerobic
oxidation of saturated carbon conjugated with pyridine moiety with an important conversion in
medicinal and synthetic organic chemistry. This eosin Y based organic transformations, exhibit a
novel approach towards site selective functionalization of pyridine with enhance integrity and
capability. This novel synthetic route may hold great potential for diverse functionalization of a
wide range of pyridine moiety with an economical and sustainable manner.
Available online
Keywords:
Visible light
Eosin Y
2009 Elsevier Ltd. All rights reserved.
Aerobic oxidation
Pyridine
The direct functionalization of pyridine using metal catalysts
or photocatalysts has been studied extensively, [1-4] due to it’s
convenient and cost-effective access to core structures of many
privileged heterocycles, which are important in materials science
[5,6] and medicinal chemistry. [7,8] The direct functionalization
of pyridine moiety remains a difficult challenge for organic
chemists, however few synthetic methods [9-14] have been
developed for alkylation of pyridine. In recent years, one of the
biggest challenges in the field of chemistry has been the
utilization of green energy and renewable processes for
photocatalytic conversion of organic compounds to provide ideal
theme in organic chemistry. [31-34] This is because solar energy
(visible light) is clean, easy to handle and an unlimited energy
source having great prospects for the development of sustainable
and eco-friendly protocols for organic synthesis. [35] Some
pioneering researchers have dedicated to converting solar energy
into chemical energy for chemical transformations [36,37] which
includes a promising strategy for the application of photoredox
catalysts to initiate single electron transfer (SET) processes.
[38,39] Visible light photoredox catalysis has recently received
much attention in organic synthesis owing to ready availability,
sustainability, non-toxicity and ease of handling. [40–45]
candidates for
a variety of environment benign organic
transformations. [15] Developing safe, accessible, and low cost
oxygen utilization for aerobic oxidation systems to access
structurally diverse oxygenated compounds is a challenging task
in catalytic chemistry. [16,17] Recently, visible-light
photocatalysis reactions have provided an attractive and energy-
saving platform for developing diverse aerobic chemical
transformations under mild conditions. [18,19] A number of
researchers have utilized and focused on photocatalytic induced
oxidation as an emerging strategy for many types of reactions,
[20-27] which have been successfully oxidized at atmospheric
pressure. The utilization of inexpensive molecular oxygen as an
environmentally friendly oxidant to develop efficient and green
protocols for visible light promoted aerobic oxidations is of great
interest in organic transformations, with high advantage area of
research. [28-30]
Harnessing visible light as a safe, renewable, and inexpensive
source of chemical energy to facilitate the construction of
Scheme 1. Photocatalysed aerobic oxidation of tertiary amines
complex organic molecules has emerged recently as a powerful
———
 Corresponding author. e-mail: ppsingh23@gmail.com

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Tetrahedron Letters
Recently,
a
superior alternative to transition metal
required for the reaction was 2 mol%. On decreasing the amount
of eosin Y from 2 mol% to 1 mol% the yield was considerably
reduced (Table 1, entry 13), whereas the yield was not enhanced
even on use of 3 mol% of eosin Y (Table 1, entry 14). The use
of another organic photocatalyst like 4CzIPN (2 mol%), rose
bengal (2 mol%), fluorescein (2 mol%), nile red (2 mol%),
perylene (2 mol%), rhodamine B (2 mol%), quinones (2 mol%)
and benzophenones (2 mol%), was not so effective as eosin Y (2
mol%) (Table 1, entry 1 versus 2 – 9). Blue LEDs [34 W, λ =
470 nm] were more effective than fluorescent light (Table 1,
entry 19), which shows that the higher photocatalytic activity of
eosin Y in presence of high intensity blue light. The presence of
O2 (air) is also essential for the reaction because only a trace of
product formation was detected under a nitrogen atmosphere
(Table 1, entry 15). Notably, the same result was obtained on
using O2 (balloon) instead of an air atmosphere (Table 1, entry
20). Moreover, the reaction was quenched with 2,2,6,6-
tetramethylpiperidyl-1-oxyl (TEMPO) (1.0 mmol) in standard
state showing that there may be radical intermediates involved in
reaction (Table 1, entry 18). Furthermore, the reaction did not
quench in the presence of DABCO (1.0 mmol) (Table 1, entry
21), which indicates the involve- ment of triplet oxygen in the
reaction. Since, DABCO is a good quencher of singlet oxygen
and quenching was not observed, it suggests that singlet oxygen
was not involved in the reaction. [66] The possibility of
substituted pyridinyl methanamine as a reducing agent that
undergoes oxidation to radical cation is very less because
quenching of radical cation could not be done. Next, the reaction
was optimized for an effective solvent system. It was found that
MeCN was the best among the tested solvents EtOH, DMF,
DMSO and MeCN, hence it was used throughout the present
study (Table 1, entry 1 versus 10 – 12).
photoredox catalysts, especially metal-free organic dyes such as
eosin Y, fluorescein, rose bengal, nile red, perylene and
rhodamine B have been used as economically and ecologically
superior surrogates for Ru(II) and Ir(II) complexes in visible-
light promoted organic transformations involving SET. [46–48]
These organic dyes have great potential for applications in
visible-light-mediated organic synthesis [49–52] which fulfils the
basic principle of green chemistry. In continuation of our work
on development of environmentally benign synthesis [53-63]
herein we report a simple, visible light irradiated, efficient green
protocol for the eosin Y catalysed aerobic oxidation of tertiary
amines conjugated with pyridine moiety (Scheme 1).
Table 1. Optimization of reaction conditions.a
Entry
Photocatalyst
Catalyst
loading
Solvent
Time
(h)
Yieldb
(%)
(mol%)
1
2
3
4
5
Eosin Y
4CzIPN
2
2
2
2
2
2
2
2
2
2
2
1
1
3
2
2
-
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
EtOH
1
1
1
1
1
1
1
1
1
1
1
1
1
1
4
4
4
4
4
1
1
93
90
87
81
79
Rose Bengal
Fluorescein
Nile Red
Perylene
Rhodamine B
Quinones
Benzophenones
Eosin Y
6
77
7
80
8
84
9
74
63
78
86
67
92
tracec
traced
n. d.e
tracef
58g
92h
89i
10
11
12
13
14
15
16
17
18
19
20
21
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
DMF
The scope of the present protocol across a range of substituted
pyridinyl methanamine incorporating various substituents. It was
found that pyridinyl methanamine with an electron-donating
group on the aromatic ring appear to react faster and afford
marginally higher yields in comparison to those bearing an
electron-withdrawing group. (Table 2)
DMSO
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
-
Eosin Y
Eosin Y
Eosin Y
Eosin Y
2
2
2
2
Table 2. Scope of the reaction.
(a) Reaction conditions: 1 (1.0 mmol), catalyst (mol%), in 3 mL solvent
irradiated using high power blue LEDs [34 W] under an air atmosphere at rt
for 1–4 h.
(b) Another one Isolated yield of the pure product 2.
(c) Reaction was performed under nitrogen.
(d) Reaction was performed in the dark.
S.N
Product
Yield
1
93
(e) Reaction was carried out without catalyst.
(f) Reaction was quenched with 2,2,6,6-tetramethylpiperidyl-1-oxyl(TEMPO)
(1.0 mmol).
(g) 34 W CFL (compact fluorescent lamp, Philips) was used.
(h) O2 balloon was used.
2a
2
3
94
90
(i) The reaction was quenched with DABCO (1.0 mmol).
2b
2c
In order to realise our idea and optimise the reaction
conditions, the key reaction of substituted pyridinyl methanamine
1a with catalytic amount of eosin Y in a solvent under irradiation
with blue LEDs [34 W, λ = 470 nm] in open air (Table 1). We
were delighted to get the desired product substituted alkyl
picolinamide 2a in 94 % yield (Table 1, entry 1). Then, the
control experiments were carried out, which show that eosin Y,
air (O2) and visible light are essential for the reaction, because in
the absence of any of the reagents/reaction parameters either the
product was not detected (n. d.) or formed in the traces (Table 1,
entry 1 versus 15 – 18). The optimum amount of eosin Y
4
5
77
85
2d
2e

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3EY* and undergoes a single electron transfer (SET). 3EY* may
6
7
8
87
undergo both reductive and oxidative quenching. [68-72] A SET
from substituted pyridinyl methanamine 1 to the excited state of
eosin Y (EY*) generates aminyl cation radical A and EY‒.
2f
88
86
72
‒
Furthermore, the reaction between oxygen and EY‧ results in
the formation of a superoxide radical anion (O2 ‒), which could
‧
then react with aminyl cation radical A to afford intermediate B.
Followed by a reaction with the hydroperoxyl radical (HOO‧ ),
2g
results the desired product 2 with elimination of water molecule.
.
The formation of superoxide radical anion (O2 −) during the
reaction was confirmed by the detection of the resulting H2O2
using KI/starch indicator. [73]
2h
9
In conclusion, we have developed
a novel, one-pot
2i
2j
photocatalysed aerobic oxidation of tertiary amines conjugated
with pyridine moiety. This protocol utilizes atmospheric oxygen
along with 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). The proposed method exhibits a new
approach towards site-selective functionalization of pyridine
derivatives and will expand the medicinal chemist toolbox for
accessing valuable privileged scaffolds.
10
11
70
76
2k
2l
12
13
14
78
95
87
Acknowledgments
We sincerely thank Emerging Science Society for financial
support as well as SAIF, CDRI, Lucknow and IISc Bangalore for
providing microanalyses and spectra.
2m
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GRAPHICAL ABSTRACT
Eosin Y Catalysed Visible-Light Mediated
Aerobic Oxidation of Tertiary Amines
Vishal Srivastavaa, Pravin K. Singha and
Praveen P. Singhb*

JOURNAL PRE-PROOF
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Highlights
 A mild and efficient one-pot visible light-
induced method
 Metal-free organic dyes have been used
 Aerobic oxidation of saturated carbon
conjugated with pyridine moiety